Method and apparatus for installation of dental implant

ABSTRACT

An organ derived from genetic material is inserted in a patient&#39;s body. Genetic material is inserted at a selected site in the body to grow an organ.

This invention relates to a method and apparatus for installing a dentalimplant in the alveolar or basal bone of a patient.

More particularly, the invention relates to a method and apparatus for adental implant which reduces the likelihood of the implant becominginfected, which does not require an opening of precise size to bedrilled or formed in the alveolar bone to receive the dental implant,which can mount an implant on existing alveolar bone without requiringalteration of the structure of the bone, which prevents the juncture ofthe dental implant and artificial tooth attached to the implant frombeing exposed in the event the patient's gums recede, which enables bonemass lost as the patient ages to be replaced, and which enables animplant to be used when drilling an opening in the alveolar bone isprecluded due to the existence of a nerve in the bone.

Dental implants are well known in the art. See, for example, U.S. Pat.No. 5,006,070 to Komatsu, U.S. Pat. No. 4,693,686 to Sendax, U.S. Pat.No. 4,812,120 to Flanagan et al., U.S. Pat. No. 4,818,559 to Hama etal., U.S. Pat. No. 4,671,768 to Ton, and U.S. Pat. No. 4,175,565 toChiarenza et al. Such prior art dental implants and methods forinstalling the same have disadvantages.

First, the implants normally must be press fit or wedged into an openingformed in the alveolar bone. Force fitting an implant into the alveolarbone is not desirable because it is uncomfortable for the patient, runsthe risk of cracking the jaw bone, further damages the bone, and, mostimportantly, increases the likelihood of infection because dentalimplants ordinarily are provided with an assortment of ridges, points,or teeth which serve as desirable sites for bacteria, both before andafter the implant is inserted in the bone. As a consequence, dentalimplants typically appear medieval.

Second, force fitting an implant in the alveolar bone requires that theopening formed in the bone have a specific size which roughly conformsto the outer dimensions of the implant so the implant can be force fitinto the opening. If a dental surgeon selects a drill of improper size,or waggles the drill while forming the hole in the alveolar bone, theimplant may not seat properly in the bone and will work free from thejaw.

Third, the surface area of the portion of the implant imbedded in thejaw is typically reduced because of the common belief that fenestrationsof various size must be formed in the implant to permit bone to growthrough and anchor the implant.

Fourth, conventional implant procedures often can not be used becausethe drilling of a opening in the alveolar bone is prohibited by a nervewhich passes through the bone.

Fifth, conventional implant procedures also often can not besuccessfully used when the jaw bone has significantly receded, as can bethe case with older patients.

Sixth, conventional implant procedures do not offer a way of replacingalveolar bone which has been lost due to aging or to some other causeresulting in injury to the bone.

Seventh, conventional implant procedures typically do not permit theready adjustment of the position of the implant after the implant isinserted in the opening formed in the alveolar bone. Correcting theposition of an improperly installed implant is often difficult, unlessthe implant is completely removed from the alveolar bone, which is atime consuming process.

Accordingly, it would be highly desirable to provide an improved dentalimplant method and apparatus which would not require the force fittingof an implant in the alveolar bone, would not require the formation of aspecific size opening in the jaw bone, would provide an implant lesslikely to loosen after being inserted in the alveolar bone, would permitan implant to be used on alveolar bone housing a nerve, would enableimplants to be successfully utilized on alveolar bone which has recededwith age, and would permit the position of the implant to be readilyadjusted after the implant is inserted in an opening in the alveolarbone.

Therefore, it is a principal object of the invention to provide animproved dental implant method and apparatus.

Another object of the invention is to provide an improved dental implantwhich can be inserted in an opening in the alveolar bone withoutrequiring that the opening must, within close tolerances, have aspecific shape and dimension.

A further object of the invention is to provide an improved dentalimplant which permits ready adjustment of the position of the implantafter the implant is placed in an opening formed in the jawbone.

Still another object of the invention is to provide a dental implantmethod which permits an implant to be attached to alveolar bone housinga nerve.

Yet a further object of the invention is to provide a dental implantmethod which allows an implant to be utilized on alveolar bone which hasexperienced significant loss and recession of its mass.

Another and further object of the instant invention is to provide animproved dental implant which is less likely to loosen after insertionin the alveolar bone.

These and other, further and more specific objects and advantages of theinvention will be apparent to those skilled in the art from thefollowing detailed description thereof, taken in conjunction with thedrawings, in which:

FIG. 1 is a front view of a dental implant apparatus constructed inaccordance with the principles of the invention;

FIG. 2 is a section view of the dental implant apparatus of FIG. 1illustrating internal construction details thereof;

FIG. 3 is a side view of a portion of the lower jaw bone illustratingthe implant of FIG. 1 installed in an opening formed in alveolar bone;

FIG. 4 is a top view of a portion of the jaw bone of FIG. 3 furtherillustrating the installation of the implant of FIG. 1 therein;

FIG. 5 is a perspective view illustrating a sheet of protective materialused to shield hydroxyapatite composition used to pack an implant intoan opening in the alveolar bone;

FIG. 6 is a top view of a portion of the lower jaw bone illustrating theinsertion of an implant in an opening formed by laterally drilling intothe jaw bone;

FIG. 7 is a side view of the jaw bone of FIG. 7 further illustrating thelateral opening formed in the jaw bone;

FIG. 8 is a side partial section view illustrating an alternateembodiment of the implant of the invention inserted in an opening formedin the alveolar bone;

FIG. 8A is a side view illustrating a portion of the implant of FIG. 8after the healing cap is removed;

FIG. 9 is a perspective view illustrating a healing cap used in theimplant of FIG. 8;

FIG. 10A is a side section view illustrating normal alveolar bonestructure around an incisor tooth;

FIG. 10B is a side section view illustrating the recession of thealveolar bone structure from around the incisor tooth of FIG. 10A;

FIG. 10C is a side view illustrating the insertion of an implant in thebone structure of FIG. 10C after the incisor tooth is removed or fallsout;

FIG. 10D is a side view illustrating the alveolar bone structure of FIG.10B after the incisor tooth is removed and a circular drill is used tocut away some of the alveolar bone to form a cylindrical anchor peg;

FIG. 10E is a side partial section view illustrating a dental implantslidably installed on the anchor peg of FIG. 10D and packed with amalleable hydroxyapatite composition;

FIG. 10F is a side partial section view illustrating the alveolar bonestructure of 10B after the incisor tooth is removed and an implant isslid onto the existing alveolar bone structure without altering thestructure;

FIG. 11 is a perspective view illustrating an implant of the type whichcan be fit to an existing alveolar bone structure;

FIG. 12 is a side partial section view illustrating a molding procedureutilized in another embodiment of the invention;

FIG. 13 is a perspective view of a sacrificial coping utilized in theembodiment of the invention illustrated in FIG. 12;

FIG. 14 is a perspective view illustrating another step in the moldingprocedure of FIG. 12;

FIG. 15 is a perspective view illustrating a finished dental bridgeproduced according to the method of FIGS. 12 and 14;

FIG. 16 is a side partial section view illustrating an artificial toothremovably attached to an implant apparatus;

FIG. 17 is a side partial section view illustrating a hip implantprocedure;

FIG. 18 is a partial side section view illustrating an interlockingopening formed in bone during an implant procedure according to theinvention; and,

FIGS. 19 to 21 illustrate an alternate implant procedure in accordancewith my invention.

Briefly, in accordance with my invention, I provide an improved dentalimplant. The implant comprises a body having a closed top and a bottomand a longitudinal axis extending through the top and bottom; and, ahead supported on the top of the body and adapted to support anartificial tooth. The body extends downwardly from the top andterminates at a lower end remote from the head. The body includes asmooth continuous surface extending from the top to the bottom anddefining the periphery of the top and the bottom. The smooth surfacecircumscribes the longitudinal axis. The body also includes a hollowcentrally defined therein, circumscribed by the continuous surface, andextending into the body through the bottom a selected distance towardthe top. The hollow only opens at the lower end of the body. The headcan have a smaller width than the body. The hollow can be an involute.The continuous surface can be shaped such that when any cross section ofthe body is taken perpendicular to the longitudinal axis, each point onthe continuous surface is generally equidistant from the longitudinalaxis.

In another embodiment of the invention, I provide a method of anchoringa dental implant in the alveolar bone of a patient. The method comprisesthe steps of forming an opening in the alveolar bone; inserting a dentalimplant in the opening, the implant comprising a body and a headsupported on the body and adapted to support an artificial tooth, thedental implant only partially filling the space in the opening; and,packing the space in the opening which is unoccupied by the dentalimplant with a hydroxyapatite composition. The opening can be largeenough to permit the implant to be readily tilted from side to sideafter insertion in the opening. After the opening is packed withhydroxyapatite composition, the implant can be adjusted or tilted fromside to side and the hydroxyapatite composition then repacked.

In a further embodiment of the invention, I provide a dental implantcomprising a body; a head supported on the body and having alongitudinal axis and including an upper portion adapted to support anartificial tooth and having a distal tip and a peripheral surfacecircumscribing the longitudinal axis and extending downwardly from thedistal tip toward the body, and, a lower portion supported on the body;and, a healing cap. The healing cap is adapted to be removably attachedto the upper portion of the head and includes a prophylactic portionwhich, when the healing cap is attached to the upper portion, slidablyextends downwardly from the tip over and covers at least a portion ofthe peripheral surface such that when the implant is inserted in anopening in the alveolar bone, a solidified filler composition at leastpartially fills the opening, extends downwardly from the distal tiptoward the body, and covers the prophylactic portion, the lower portion,and the body, and the healing cap is removed from the head, a spaceexists intermediate the portion of the peripheral surface and thesolidified filler composition such that an artificial tooth can extendinto the space and cover the distal tip of the head. The fillercomposition can be a hydroxyapatite composition.

In still another embodiment of the invention, I provide a method ofanchoring a dental implant to the alveolar bone of a patient. The methodcomprises the steps of placing the dental implant at a selected site onthe alveolar bone, the dental implant comprising a body and a headsupported on the body and adapted to support an artificial tooth;packing a malleable hydroxyapatite composition around the dental implantand against alveolar bone of the patient; and, covering the malleablehydroxyapatite composition with a pliable sheet of material to at leastpartially prevent gum tissue from growing into the hydroxyapatitecomposition while the hydroxyapatite composition solidifies.

In yet another embodiment of the invention, I provide a dental implantfor a ridge of alveolar bone normally at least partially covered by gumtissue. The implant comprises a body having a top and a pair of opposedfeet each extending downwardly from the top to a tip at a lower endremote from the top, the feet having an inner surface shaped, contoured,and dimensioned to conform to the ridge of alveolar bone when the gumtissue is removed from the ridge; and, a head supported on the body andadapted to support an artificial tooth.

In yet still another embodiment of the invention, I provide a method ofanchoring a dental implant to the existing alveolar bone of a patient,the bone having an existing outer surface. The method comprises thesteps of removing alveolar bone to form an outwardly projecting anchorpeg having a selected shape and dimension; and, inserting a dentalimplant over the anchor peg. The dental implant comprises a body and ahead support on the body and adapted to support an artificial tooth. Thebody extends downwardly from the head to a lower end remote from thehead and having an aperture formed in the lower end. The aperture isshaped and dimensioned to be slidably inserted on and conform to theoutwardly projecting anchor.

Turning now to the drawings, which depict the presently preferredembodiments of the invention for the purpose of illustrating thepractice thereof and not by way of limitation of the scope of theinvention and in which like reference characters refer to correspondingelements throughout the several views, FIG. 1 illustrates dental implantapparatus which is constructed in accordance with the principles of theinvention and includes a dental implant which has the general shape of awine bottle and includes a cylindrical head 10 attached to a body 11.The closed top 12 of body 11 has a smooth continuous conical outersurface which tapers from the smooth continuous outer cylindricalsurface 14 of the bottom 11 into the smooth cylindrical outer surface 13of head 10. The conical outer surface of top 12, as do smoothcylindrical surfaces 14 and 13, completely circumscribes longitudinalaxis and centerline 18. Head 10 can, if desired, be bent at someselected angle with respect to axis 18 and body 11 as indicated bydashed lines 10B or can be tapered in the manner of head 10A in FIG. 12.The bottom of body 11 extends downwardly from the top 12 and terminatesat lower end 17 remote from the head 10. Involute or hollow 15 is formedcentrally within body 11, is circumscribed by continuous surface 14, andextends upwardly into body 11 a selected distance toward top 12. Hollow15 opens only at the lower end 17. Head 13 has a smaller diameter thanbody 11. An internally threaded aperture 19 is formed in-head 13 toreceive the externally threaded end 20 of a healing cap. Thefrustroconical head 21 of the healing cap has a cylindrical aperture 22formed therein. Cylindrical member 23 is attached to pliable fabricsheet 24 and is shaped to be removably snap fit into aperture 22. Thesheet 24 can be secured to the healing cap or head 10 using anyconvenient means. For example, an aperture 25 can be formed through apliable sheet 24 A and sized such that end 20 slides through aperture 25and permits sheet 24 A to be compressed between head 21 and the circulardistal end 26 of head 10. Rib 16 outwardly depends from the smoothcylindrical wall circumscribing and defining hollow 15 and, when hollow15 is filled with hydroxyapatite or bone in a manner which will bedescribed, prevents the dental implant from rotating about axis 18. Mostinfection in a tooth begins at the gum line and works its way downwardlytoward the root of the tooth. The smooth continuous outer surfaces 13,14 of the implant of FIG. 1 facilitate determining how far, if at all,infection has penetrated downwardly along the outer surfaces of theimplant. The extension of the outer surfaces of the implant from thedistal end 26 of the head to the lower end 17 make it difficult forinfection to enter hollow 15. In many conventional implants, onceinfection extends a short distance into the bone, it is a simple matterfor the infection to spread laterally under portions of the implant.Consequently, in the implant of FIG. 1 it is important that perforationsare not formed through the continuous outer surfaces 13, 14, or theconical surface of top 12. The large area of surfaces 13 and 14 and ofthe outer conical surface of top 12 help distribute the forces which areproduced on an artificial tooth mounted on the implant and decrease thelikelihood that the implant will come loose. The smooth curvature andlack of ridges or points extending outwardly from implant surfaces 13and 14 also decreases the likelihood that stress fractures will beformed in the alveolar bone during the use of an artificial toothattached to the implant.

The installation of the implant apparatus of FIGS. 1 and 2 in alveolarbone is illustrated in FIGS. 3 and 4. As shown in FIG. 4, an opening 27is drilled or otherwise formed at a selected location in the alveolarbone and the dental implant is inserted in opening 27. FIG. 4illustrates opening 27 immediately after the dental implant has beeninserted therein. Opening 27 is larger than the dental implant so thatthe head 10 can be rasped manually or with a dental instrument andtilted from side to side in opening 27. The space between the dentalimplant and the sides of opening 27 which circumscribe the implant ispacked with a malleable hydroxyapatite composition 28. Hollow 15 canalso be packed with the hydroxyapatite composition 28 before the implantis inserted in opening 27. After the composition 28 is packed intoopening 27 around the dental implant, the head 10 can, if desired, belaterally moved in directions like those indicated by arrows A to tiltand reposition the implant in opening 27. After the dental implant is inthe desired position in opening 27, the hydroxyapatite composition isrepacked, and member 23 is snapped into aperture 22 in head 21 toposition sheet 24 over opening 27 in the manner illustrated in FIG. 3.Sheet 24 can be trimmed as appropriate to cover opening 27. Although notshown in FIG. 4, gum tissue ordinarily at least partially covers andhelps maintain sheet 24 in its desired position. Sheet 24 can compriseGORTEX or any other suitable pliable material which helps prevent gumtissue from growing into the hydroxyapatite composition while itsolidifies. If desired, sheet 24 can comprise a resorbable material. TheGORTEX is left in place for a period of two to twelve months while thesurrounding bone grows into and causes the hydroxyapatite composition tosolidify and anchor the dental implant in place. After thehydroxyapatite composition has solidified, the healing cap and the sheet24 are removed such that the gum tissue covers the solidifiedhydroxyapatite composition. The internally threaded aperture 19 in thehead 10 of the implant is used to attach an artificial tooth to theimplant.

GORTEX is produced by W. L Gore & Assoc., Inc. Regenerative Technologiesof 3773 Kaspar Avenue, Flagstaff, Ariz. 86003-2500, USA. If desired, apliable sheet 24A can include a layer of GORTEX or similar pliablematerial laminated with an undercoating of collagen, polyglycolic acid,or another desired material. The collagen imparts a stiffness to sheet24A and over time is gradually dissolved by the body.

GORTEX is an expanded polytetrafluroethylene (e-PTFE) material.

Hydroxyapatite is a crystalline substance containing calcium andphosphorus and is found in certain rocks. It is the basic constituent ofbone. The hydroxyapatite composition used to pack opening 27 can simplycomprise a dry hydroxyapatite powder. The hydroxyapatite is, however,normally mixed with a liquid substance to form a slurry or moremalleable composition which is more readily packed and remains in fixedposition than dry bydroxyapatite powder. Hydroxyapatite powder can bemixed with water, plaster, collagen, dextran, epinephrine, or some otherdesirable material. The hydroxyapatite can be obtained from naturalmineral sources, from ground bone, etc. Materials other thanhydroxyapatite compositions can be used to fill and pack opening 27.Such other materials can include organic and inorganic matrices and/orcombinations thereof. These matrices can be porous, non-porous, activeand/or resorbable matrices, or totally inert. For example, coral andcoral analogs, polymethyl methacrylate, polyethylene, PTFE(polytetrafluroethylene), polysufone, polymers, polyethylene glycols,osteomin (bone ash), autogenous bone, freeze dried demineralized bone,resorbable and non-resorbable hydroxyapatite, xenographs (bovine),miniscrews, allografts, composites, polyethylene glycol propionaldehyde,HAPSET, or the patient's own bone can be utilized.

In some cases, it is preferable to produce an opening for a dentalimplant by forming an aperture in the alveolar bone which openslaterally or outwardly away from the inside of the patient's mouth. Suchan outwardly opening aperture 32 is illustrated in FIGS. 6 and 7. InFIG. 7, the dental implant has not yet been inserted on floor 33 ofaperture 32. FIG. 6 illustrates the implant in aperture 32. A malleablehydroxyapatite composition is utilized to pack the dental implant inaperture 32. Once aperture 32 is packed with hydroxyapatite compositionand the implant is properly positioned in the hydroxyapatite compositionand aperture 32, a healing cap is used to attach a pliable layer 24 ofmaterial to head 10 to protect the hydroxyapatite composition frominvasion by epithelial or other living tissue while the compositionhardens. After an appropriate period of time has passed and the bone hasgrown into and hardened the hydroxyapatite composition, the healing capand layer of material are removed and an artificial tooth is attached tohead 10 using internally threaded aperture 19.

An alternate embodiment of a healing cap 34 is illustrated in FIGS. 8and 9. Cap 34 includes internal cylindrical aperture 35 shaped toslidably fit over the circular distal end 26 of head 10 and to cover atleast a portion of the cylindrical peripheral surface 13 of head 10 ofthe wine bottle shaped implant of FIG. 1. The pliable sheet 24 in FIG. 8has a circular aperture 37 formed therethrough which is large enough toslide a selected distance up the conical tip of cap 34, in the mannershown in FIG. 8, but which is too small to slide over the cylindricalupper end 39 of cap 34. Consequently, the conical end 40 of cap 34functions to hold the sheet 24 in position against the hydroxyapatitecomposition 28 in the manner illustrated in FIG. 8. Further, a portionof the conical end 40 of cap 34 extends downwardly along surface 13 andpast end 26 so that after the composition 28 has solidified and cap 34is removed from head 10, a conically shaped space 41 (FIG. 8A) existsintermediate the solidified composition 28 and the upper portion ofsurface 13. When an artificial tooth 50 is subsequently attached to head10 using the internally threaded aperture 19 formed therein, the lowerportion of tooth 50 can include a cylindrical aperture 51 which slidesover the upper end of head 10 and covers distal end 26. As would beappreciated by those of skill in the art, either sample implants orimpression analogs of the head 10, 10A (FIG. 12) of the support member70 (FIG. 12) of each implant can be provided to a dental laboratory sothat the lower margins of an artificial tooth 50 can be perfectly sizedto extend into and completely fill the conically shaped space 41. Distalend 26 ordinarily is positioned at the gum line after the implant isinserted in an opening 38 formed in the alveolar bone. Accordingly, theportions of the artificial tooth 50 extending into space 41 extend belowthe gum line of the patient.

FIG. 10A illustrates a normal, healthy alveolar bone 52 supporting anincisor tooth 53. In FIG. 10B, the bone 52 has receded due to age orother factors. In FIG. 10C, tooth 53 has been removed; a cylindricalaperture 54 has been drilled or otherwise formed in the bone 52; animplant has been inserted in aperture 54; a malleable hydroxyapatitecomposition 28 has been packed into aperture 54, around the implant, andagainst the bone 52; a layer of pliable material 24 has been attached tohead 10 with the head 21 of a healing cap and extends over thehydroxyapatite composition 28; and, the gum tissue has been positionedover material 24. After the bone 52 grows into the hydroxyapatitecomposition 28 and the composition 28 solidifies, the healing cap andmaterial 24 are removed, and an artificial tooth is attached to head 10.The hydroxyapatite composition applied to the implant and bone 52 inFIG. 10C is used to augment or build the bone 52 back up to a shape anddimension resembling or duplicating its original normal shape anddimension illustrated in FIG. 10A. A particular advantage of the dentalimplant methodology of the invention is that it permits hydroxyapatitecompositions to be used to augment and enlarge existing alveolar bonestructure while at the same time facilitating the anchoring of animplant to alveolar bone. To facilitate the anchoring of an implant inthe existing alveolar or basal bone, indents or grooves can be formed inthe bone or in the surface of the implant to receive hydroxyapatite orother material used to fill or pack into or around the alveolar or basalbone and the implant.

In FIG. 10D, the tooth 53 has been removed from the alveolar bone 52 ofFIG. 10B and a circular drill has been used to remove some of the bone52 to form a cylindrical anchor peg 56 which is shaped and dimensionedto be slidably received by the involute 15 of the implant of FIG. 1 inthe manner illustrated in FIG. 10E. After involute or hollow 15 is slidonto peg 56, malleable hydroxyapatite composition is packed around thebody 11 and head 10 of the implant and the head 21 of the healing cap isused to attach pliable material 24 to head 10. If desired,hydroxyapatite composition 28 can also be inserted in hollow 15 beforehollow 15 is slid onto peg 56. One the hydroxyapatite composition hassolidified, the healing cap and material 21 are removed, and anartificial tooth is attached to head 10. The bone 52 illustrated inFIGS. 10D and 10E includes a nerve 65.

In FIG. 10F, the tooth 53 has been removed from the alveolar bone 52 ofFIG. 10B and shape of the ridge 64 of bone 52 has not been altered. Animplant has been placed on ridge 64. The implant includes head 61, body62, and arch or U-shaped aperture 63. Aperture 63 is shaped anddimensioned to conform to and slide on to ridge 64 in the mannerillustrated in FIG. 10F. The implant of FIG. 10F can be formed by makinga mold of ridge 64 and using the mold to eventually produce an implantwith an aperture 63 which will conform to ridge 64. Various techniquesfor making a mold of ridge 64 and using the mold to produce a duplicateof the ridge or to produce a shape which will conform to the ridge 64are well known in the art and will not be discussed herein. After theimplant of FIGS. 10F and 11 is slidably inserted on ridge 64 in themanner shown in FIG. 10F, malleable hydroxyapatite composition ispressed against and molded around against the implant and bone 52 andcovered with a layer 24 which is secured to head 61 by head 21 of thehealing cap illustrated in FIG. 1. The externally threaded end 20 of thehealing cap is rotated into internally threaded aperture 67 formed inthe upper end of head 61. If desired, an aperture(s) 68 can be formedthrough body 62 to permit a screw(s) to pass through the aperture 68 andinto the bone 52 to secure the implant to the bone 52. In addition, aslot, indicated by dashed lines 66 in FIG. 10F, can be cut through ridge64 to receive a panel 69 which is attached to arch 63 in the positionindicated by dashed line 70.

FIGS. 12 to 15 depict apparatus using in a molding method which is usedin conjunction with the implant apparatus and methodology of theinvention. In FIG. 12, an implant having a head 10A and bottom 11A isheld in position in opening 79 formed in alveolar bone by a solidifiedhydroxyapatite composition 28. Composition 28 solidified when thesurrounding alveolar bone 80 grew into the composition 28 in opening 79.Head 10A has a conical head which tapers upwardly from body 11A towardthe gum tissue 81. Head 10A has outer smooth continuous surface 13A.Body 11A includes outer smooth continuous surface 14A. Frustoconicalsupport member 70 is attached to head 10A. Sacrificial frustoconicalcoping 71 is slid over member 70. Sacrificial frustoconical coping 74 isslid over member 73. If desired, copings 71 and 74 can be metal and notbe sacrificial. Member 73 is attached to the head 10A (not shown) ofanother implant (not shown) in the alveolar bone 80. Rubber, silicone,or some other acceptable material is used to form a negative mold 72extending over and around copings 71 and 74 in the manner shown in FIG.12. The use of such molding materials in dentistry is well known andwill not be discussed herein. The negative mold includes upstandinghollow conical member 85; frustoconical hollows 83 and 84 which conformand adhere to copings 71 and 74, respectively; and, surfaces 86 and 87which conform to gum tissue 81. When the negative mold 72 is removedfrom members 70 and 73, copings 71 and 74 are removed with and areimbedded in the mold 72.

After mold 72 has set and is removed from members 70 and 73 and from thepatient's mouth, mold 72 is used to make a positive stone mold 78. Thisis, as is well kmown, accomplished by inverting mold 72, place mold 72in a container which circumscribes mold 72, and by pouring a stone moldslurry into sacrificial copings 71 and 74 and over surfaces 86 and 87.After the stone mold slurry hardens to form mold 78, the mold 78 andmold 72 are heated until mold 72 melts and flows off of stone mold 78,or, mold 72 can simply be peeled off of the hardened stone mold with orwithout copings 71 and 74. The positive stone mold 78 which remainsreplicates the gum line 81, support members 72 and 73, and the upperportion of each head 10A as shown in FIG. 12. The stone mold 78 alsoreplicates 82A the conical groove or detent 82 formed around the upperportion of each implant head 10A. In FIG. 14, each conical groove 82 hasa shape and dimension equal to the shape and dimension of conical groove82 in FIG. 14. Also, in FIG. 14, the portions of the stone mold whichreplicate frustoconical members 70 and 73 are not visible because newsacrificial copings 71A and 74A have been slipped over said portions ofthe stone mold (or the copings 71 and 74 which were originally used inthe mouth to make mold 72 can remain on said portions of the stonemold). While the shape and dimension of each coping can vary, in FIGS.12 to 14, each coping 71, 74, 71A, 74A is of equivalent shape anddimension. The shape and dimension of each support member 70 and 73 canalso vary as desired. In FIG. 12, however, each frustoconical supportmember 70 and 73 is of equal shape and dimension.

In FIG. 14 a pontic comprised of frustoconical support member 77 andribs 75 and 76 has been constructed above the upper surface 90 of stonemold 78. The pontic interconnects sacrificial copings 71A and 74A and ispositioned adjacent surface 90. The pontic is typically constructed fromwax, but any other desired material can be utilized. Once theconstruction of the pontic is completed, the sacrificial bridge supportof FIG. 14 is removed from mold 78 and mold 78 is discarded, or, mold 78is retained for use in subsequent porcelain work. After the sacrificialbridge support is removed from mold 78, its shape and dimension andappearance is identical to that of the finished metal bridge supportpictured in FIG. 15.

In the next step of the molding process, the sacrificial bridge supportis submersed or “invested” in a stone mold slurry and, before or as theslurry hardens, a small escape channel is formed which leads from thesacrificial bridge support through and to the upper surface of theslurry. After the stone mold slurry hardens, it is heated to melt thewax pontic and the sacrificial copings 71A and 74A. The melted wax andmelted materials from the copings 71A and 74A flows out of the stonemold through the escape channel. After all of the melted material flowsout of the stone mold, a hollow exists in he stone mold which is anegative of the sacrificial support bridge of FIG. 14 and of the ridgeof FIG. 15. The investment molding process is continued by pouringmolten metal through the escape channel into this hollow and allowingthe metal to harden. After the metal hardens, the finished supportbridge of FIG. 15 has been formed in the stone mold. The stone mold isbroken away from the bridge to free the finished bridge from the mold.Porcelain or another desired material is placed on the bridge supports74B, 77A, and 71B to build artificial teeth on the bridge. Ordinarily, asingle artificial tooth is built on each bridge support After artificialteeth are constructed on the bridge supports, the bridge is inserted inthe patient's mouth by placing hollow support 71B over member 70 and byplacing hollow support 74B over member 73. Supports 74B and 71B can beglued or otherwise affixed to members 73 and 70, respectively.

A method of removably attaching a bridge support 74B and artificialtooth 91 to a member 73 is illustrated in FIG. 16. In FIG. 16 a fastener94 is inserted into aperture 92 and threaded into internally threadedaperture 93 in member 73. Precise alignment of apertures 92 and 93 isnot required because the diameter of aperture 92 is slightly larger thanthat of aperture 93. The undersurface 95 of fastener conforms to andbears against a portion of conical surface 96 to prevent the tooth 91from moving in the directions of arrows B. When fastener 94 is removedfrom apertures 92 and 93, coping 74B can be pulled upwardly off of andfree from support member 73.

In FIG. 16, the upper distal end 26 A of head 10A contacts the bottom ofsupport member 73. The outer peripheral conical surface of head 10A iscontiguous with and lies in a common conical plane with the outerconical surface 13A of head 10A. Coping 74B conforms to surface 13A andto the outer conical surface of member 73 so that coping 74B slidablyengages and fits said conical surfaces in the manner illustrated in FIG.16. The co-planar relationship of the conical surface of member 73 andthe conical surface 13A of member 10A is important in the practice ofthe invention because it enables coping 74B and tooth 91 to extendsealingly downwardly below the gum line, i.e. to extend downwardly belowend 26A.

Members 70 and 73 can be fabricated from metal or from plastic, rubber,copolymer, polymer, composites, or any other desired material, as canthe sacrificial copings 71, 74, 71A, 74A.

The implant method and apparatus of the invention have severaladvantages. First, since the opening which is formed in the bone toreceive the implant does not have to conform to the shape and dimensionof the implant, special drills are not necessary when the opening isformed in the alveolar or basal bone to receive the implant. Second,drilling an opening in the bone which is larger than and does notconform to the shape and contour of the implant decreases the amount ofheat generated during the drilling process. This is important becausebone is damaged when exposed to heat in excess of 130 degrees centigradefor one minute or more. Conventional implants require that a cylindricalopening be drilled in the bone. Drilling such openings requires the useof internally irrigated slowly rotating burrs and is more likely togenerate heat which damages the bone adjacent the cylindrical opening.When an opening is drilled for the implant of the invention, a higherspeed externally irrigated burr can be utilized. Third, the implant ofthe invention permits non-resorbable hydroxyapatite to be utilized tofill in the opening around the implant. The non-resorbablehydroxyapatite produces a strong, tough structure which is less likelyto have saucerization. Saucerization occurs when bone is lost fromaround the implant due to stress or bacterial invasion. This use ofnon-resorbable hydroxyapatite is particularly advantageous when a boneridge which has receded is being augmented to duplicate the originalshape and size of the ridge. Fourth, the lateral insertion of an implantin the manner illustrated in FIGS. 6 and 7 is useful in the case where atooth has been missing for some time and adjacent teeth have migratedinto and partially filled the space of the missing tooth. When thisoccurs, conventional implants either are forced to be so small that theyare weak or are prevented from being utilized due to the small size ofthe space remaining between the adjacent teeth. The implant of FIGS. 1and 8 solves this problem because it has a large base with a thin neckwhich can extend between the remaining adjacent teeth. Fifth, theimplant method of the invention covers the junction between a supportmember 70 and the head 10A (FIG. 12) of the implant. In conventionalimplants, this junction is exposed to oral fluids and can corrode andfail. Further, dentists often do not screw or otherwise install member70 snugly against the top of head 10A, leaving a septic gap. Sixth, theimplant of FIGS. 1, 8 and 12 can be long or short and still provide alarge outer surface area for anchoring the implant in the alveolar orbasal bone.

As would be appreciated by those of skill in the art, the implantmethodology described above in connection with dental implants can beutilized to carry out implants in bone throughout the body. For example,in FIG. 17, the “ball” at the top of femur 100 has been removed and anoversized opening 101 has been formed in the top of femur 100. Implant103 is inserted in opening 101. The lower portion of implant 103 is thebody thereof and the upper portion of implant 103 (the portion nearestartificial “ball” 105) is the head of the implant 103. Each implant inthe prior art and illustrated herein includes a lower portion, or body,and an upper portion, or head. A hydroxyapatite (HA), hydroxyapatitecement (HAC) or other composition 102 is packed around implant 103 tosecure implant 103 in opening 101. An internally threaded cylindricalaperture (not visible) is formed in implant 103 to receive theexternally threaded end 104 of an artificial “ball” 105. It isadvantageous to form opening 101 by laterally cutting or drilling intothe top of femur 100 in the manner illustrated in FIG. 6. This reducesthe amount by which the femur has to be laterally displaced away fromthe hip socket during formation of opening 10, thus reducing trauma tosurrounding nerves, muscles, blood vessels and soft tissue.

In FIG. 18, the opening 108 in bone 107 and the implant 106 are shapedand dimensioned such that when implant 106 is laterally slid intoopening 108, a mechanical lock is formed and implant 106 cannot beremoved from opening 108 in the direction of arrow C. Similarly, opening108 and implant 106 can be formed such that implant 106 is inserted inopening 108 in the direction directly opposite that of arrow C and isrotated 90 degrees about an axis parallel to arrow C such that afterimplant 106 is so rotated, it cannot be displaced out of opening 108 inthe direction of arrow C because the longer dimension of implant 106 hasbeen turned to a position similar to that shown in FIG. 18 under theinwardly extending lips 109 and 110 of opening 108.

The opening 108 illustrated in FIG. 18 can be formed and an implantinserted in opening 108 which flares outwardly like implant 106 butwhich can be readily withdrawn from opening 18 in the direction of arrowC. The implant is anchored in opening 108 by packing HA, HAC, or anothercomposition in opening 108 and around implant 106. The composition 102used to pack around an implant 103 can include magnetic fibers and havea viscosity which permits the fibers to align when a magnetic force isapplied to the composition. The composition 102 can also, in combinationwith the magnetic fibers or in place of the magnetic fibers, includefibers which do not respond to the magnetic force.

As noted earlier, active compositions can be utilized in combinationwith or in place of hydroxyapatite compositions. Such activecompositions, or tissue growth factors, can be intermixed withhydroxyapatite or other materials utilized as packing around an implant,can be coated on an implant 103, or can be inserted in situ intermediatethe implant 103 and opening 101 to cause, for example, the bone to growback inwardly toward the implant. In the event implant 103 is coatedwith a bone growth factor or a bone growth factor is inserted in situintermediate an implant 103 and opening 101 in the bone, positioningmeans can be utilized to maintain implant 103 in its desired position inopening 101 until bone ingrowth contacts implant 103 and maintains it inposition. The positioning means can also be utilized to maintain animplant in position until a filler material is packed in opening 101around the implant to anchor the implant in position. Such positioningmeans can consist of a collar or template which fixedly and/orresorbably contacts or supports implant 103 and is anchored tosurrounding bone or other tissue. The positioning means can also consistof a putty or gel which is packed around the implant 103 to maintain itin position while bone grows into the putty or gel and to the implant oruntil the putty or gel sets up. Once bone ingrowth secures implant 103in its desired position, the collar or template which is used to supportthe implant is removed or is resorbed. Resorption of the collar orimplant can occur according to the natural physiological process of thebody or can be triggered and/or facilitated by external means such asheat, electricity, enzymes injected into tissue, etc.

By way of further example of the template just referred to, an implantto replace a missing first molar in the lower jaw of a patient iscarried out as follows. First, the space between the second premolar andthe second molar which bounded the missing first molar may be laserscanned or an impression taken to define the space so that the shape anddimension of the tooth which will fill the space can be defined. Animpression is taken of the lower teeth and a plaster model of the lowerteeth is made using well known molding techniques. This plaster model,as does the patient's mouth, includes on open spot which at one time wasoccupied by the patient's missing first molar. A model is made of theartificial tooth which will be mounted on the implant. The model isproperly positioned in the open spot in the plaster model and aimpression is made of the plaster model using plaster, plastic or anyother desired material. This plastic model will fit over and conform tothe lower teeth in the patient's mouth. An opening is formed through theplastic model and an externally threaded screw or other attachment meansis attached through and extends downwardly from the plastic model sothat the implant which will be utilized in the mouth of the patient canbe detachably secured to the externally threaded screw. The externallythreaded screw positions the implant in the exact desired orientation,both laterally and vertically, with respect to the plastic model andwith respect to the opening formed in bone in the patient's mouth (orwith respect to bone in the patient's mouth on which the implant isset). An oversized opening 27 (FIG. 3) is drilled in the alveolar bone.The bottom of the opening is prepacked with a selected amount ofhydroxyapatite or other composition. The implant 11 is threaded onto theexternally threaded screw in the plastic model and the plastic model isfit over the crowns of the patient's lower teeth to force the implant 11into the opening 27 and force the hydroxyapatite composition up andaround the implant 11. Openings can be formed in and through the plasticmodel to permit hydroxyapatite composition to be added to or removedfrom opening 27. Or, in the event implant 11 is simply coated with abone or tissue growth factor, openings need not be formed through theplastic model to permit access to opening 27 because the plastic modelpositions the implant 11 in the exact desired location in opening 27 andmaintain the implant 11 in that position until the tissue growth factorcauses an outgrowth of new bone from opening 27 which contacts andanchors implant 11 in position. The coating of bone or tissue growthfactor can occur just prior to insertion of the implant, after theimplant is inserted, or well prior to insertion of the implant. Afterthe implant 11 is anchored by the growth of new bone toward the implant,the externally threaded screw is turned out of the implant, the plasticmodel is removed and an artificial tooth can be threaded into orotherwise attached to the anchored implant 11. After (of before, ifdesired) the artificial tooth is attached to implant 11, a tissue growthfactor can be applied around the implant to the surface of the implant,to the surface of bone around implant 11, or to gum tissue to promotethe growth of gum tissue over the surface of the bone and adjacent theartificial tooth.

Growth factors can be utilized to induce the growth of “hard tissue” orbone and “soft tissues” like ectodermal and mesodermal tissues. As usedherein, the term growth factor encompasses compositions and livingorganisms which promote the growth of hard tissue, such as bone, or softtissue in the body of a patient. The compositions include organic andinorganic matter. The compositions can be genetically produced ormanipulated. The living organisms can be bacteria, viruses, or any otherliving organism which promote tissue growth. By way of example and notlimitation, growth factors can include platelet-derived growth factor(PDGF), epidermal growth factor (EGF), fibroblast growth factor(acidic/basic)(FGF a,b), interleukins (IL's), tumor necrosis factor(TNF), transforming growth factor (TGF-B), colony-stimulating factor(CSF), osteopontin (Eta-1 (OPN), platelet-derived growth factor (PDGF),interferon (INF), bone morphogenic protein 1 (BMP-1), and insulin growthfactor (IGF). Recombinant and non-recombinant growth factors can beutilized as desired. Bacteria or viruses can, when appropriate, beutilized as growth factors. For example, there is a bacterialhydrophilic polypeptide that self-assembles into a nanometer internaldiameter pore to build a selective lipid body. Various enzymes can beutilized for the synthesis of peptides which contain amino acids thatcontrol three-dimensional protein structure and growth. Growth factorscan be applied in gels or other carriers which regulate the rate ofrelease of the growth factors and help maintain the growth factors, andthe carrier, at a desired location in the body. Time release capsules,granules, or other carriers containing growth factor can be activated bytissue pH, by enzymes, by ultrasound, by electricity, by heat, byselected in vivo chemicals or by any other selected means to release thegrowth factor. The carrier can be resorbable or non-resorbable. Or, thegrowth factor itself can be activated by similar means. Either thecarrier or the growth factor can mimic extracellular fluid to controlcell growth, migration, and function. The growth factor can beadministered orally, systemically, in a carrier, by hypodermic needle,through the respiratory tract, or by any other desired method. Thegrowth factor can also be administered into a capsule or other man-madecomposition or structure placed in the body. While administration of thegrowth factor is presently usually localized in the patient's body,circumstances may arise where it is advantageous to distribute a growthfactor throughout the patient's body in uniform or non-uniformconcentrations. An advantage to growth factors is that they can often,especially when in capsule form or in some other containment system, beinserted to a desired site in the body by simply making a small incisionand inserting the growth factor. The making of such a small incisioncomprises minor surgery which can often be accomplished on anout-patient basis. The growth factors can be multifactorial andnonspecific.

A variety of collagen materials can be used alone and in combination(Types 1 to 12) to form a containment sock, pocket or other structurefor a growth factor, which structure may have useful features ofcontrolled degradation and porosity for tissue reconstruction. Otherknown naturally occurring materials such as biopolymers, cross-linkedprotein scaffolds, and gels can be used alone or in combination witheach other or with any other material to form a containment system forhydroxyapatite or other tissue augmentation materials. A containmentpocket or other structure can be formed with synthetic organic materialssuch as polymers or plastics, with natural inorganic materials (e.g.,hydroxyapatite and other ceramics), with organic materials (e.g.,biopolymers), or with synthetic inorganic materials.

Possible polymers usable in a pocket or other containment structureconstructed in accordance with the invention include, withoutlimitation, poly (Amides), poly(Esters), poly(Orthoesters),poly(Anhydrides), poly (Ureas), poly(Orthoesters), poly(Anhydrides),poly(Ureas), poly(Alkyl 2-Cyanoacrylates), poly(Dihydropyrans),poly(Acetals), poly(Phosphazenes), and poly(Dioxinones). Each of theforegoing polymers is biodegradable in natural systems by undergoing ahydrolytic, enzymatic, or other breakdown or degradation and, as such,is capable of providing biodegradable matrices, scaffolds and otheruseful structures of a containment structure. Examples of biodegradablepolyamides include glutamic acid, glutamic acid/leucine, biodegradablenylon, glutamic acid/ethyl glutamate, hydroxyalkyl-L-glutamine, andcollagen. Examples of biodegradable polyesters include D, L lactic acid,glycolic acid/lactic acid, L-lactic acid, caprolactone/D,L lactic acid,diglycolic acid/transcyclonhexanedimethanol, and polyesterhydrogels.

In one embodiment of the packing material 102 used in the invention,hydroxyapatite is mixed with a biodegradable polymer, with or without agrowth factor impregnated therein, to provide a composition whichresists penetration by epithelial tissues but which promotes growth ofadjacent bone or soft tissue structure.

In a further embodiment of the invention, a pocket or other containmentstructure is fabricated from a microporous material containing a drug orother agent in its pores which promotes the growth of living tissue. Thepore sizes can be in the range of 25 to 400 microns, or can have anydesired size. The containment structure can be positioned in an opening101, adjacent selected soft tissue or bone, or at any other location inthe patient's body.

In another embodiment of the invention, hydroxyapatite or another tissueaugmentation material is mixed with a material to produce a mixturewhich is sensitive to ultraviolet light and which hardens and sets afterbeing dispensed at a desired location intermediate the tissue andunderlying bone. UV light is delivered by fiber optic means to thelocation at which the augmentation material is dispensed intermediatetissue and underlying bone. The UV light promotes the hardening orsetting up of the tissue augmentation material.

In still another embodiment of the invention, a volume of tissueaugmentation material is provided with a coating which resists migrationfrom the tissue augmentation material of tissue augmentation drugs orother growth factors or materials. The coating can be biodegradable andbreak down over time.

The hydroxyapatite (HA) and hydroxyapatite cement (HAC) compositionswhich can be utilized to pack around implants in accordance with theinvention are inorganic, crystalline materials. The hexagonal rhombicprism structure and calcium and phosphate composition of HA's and HAC'sare very similar to the natural ceramic hydroxyapatite mineral thatmakes up the inorganic portion of bone and teeth. HA's and HAC's arebioactive and interact with bone and teeth by forming a directphysicochemical bond with these hard tissues. Consequently, HA's andHAC's are osteoconductive and initiate bone ingrowth. HA's and HAC's canalso harbor osteoinductive material like osteocalcin which helps formnew bone cells. A distinct advantage of HAC's is that they can, whilestill in a relatively low viscosity state, be interposed between animplant and opening in the bone to readily conform to implant and bonesurfaces. Neither RAC's or HA's generate any appreciable heat when usedto pack around an implant. HAC's and HA's can be mixed with bodilyfluids.

HAC'S, HA's, growth factor compositions, and other packing compositionsused to pack around an implant can be formulated to expand after beinginserted intermediate an implant and surrounding bone. Such expansion isadvantageous because after an opening is cut in bone, the bone adjacentthe opening tends to shrink “away” from the opening, enlarging theopening. By way of example, an HAC packing composition can be formulatedto expand by intermixing a gas generating material or a material with athermal coefficient of expansion with the packing composition. The gasgenerating material forms pores in the packing composition and causes itto expand. The gas generated is preferably carbon dioxide, nitrogen, oranother inert gas is preferred. The gas generating or expandablematerial can be resorbable. If desired, the packing composition can beaerated with a gas before it is inserted in an opening to anchor animplant in place. Polyethylene has a coefficient of thermal expansion ofabout 0.00018 per degree Centigrade. Polyethylene or another polymermaterial with a preferred coefficient of thermal expansion can beutilized as a component in the packing composition. Or, the packingcomposition can include a liquid component which expands when the liquidcomponent sets and solidifies.

In one embodiment of the invention, a dental implant and crown aredesigned to custom fit in the alveolar bone and efficiently dissipateocclusal stress generated during use of the crown to chew food. Implantsother than dental implants can also be designed using the followingprinciples.

A ruler, X-ray, laser scanner, impressions of the teeth and jaws, orother means are used to define the shape and dimension of the space tobe occupied by the artificial crown which is attached to the implant andto define the shape and dimension of the alveolar bone in or on whichthe implant is to be positioned. A force diagram can be generated whichdefines how the roots of each original tooth in the mouth of anindividual dissipate the stresses generated on the tooth during chewingand/or biting. Similarly, a force diagram can be generated defining anoptimal root design for uniformly dissipating stress into alveolar bone,for dissipating more stress into stronger areas of the alveolar bone,etc. Such an optimal root design is ordinarily arrived at with the useof a computer and is important because many dental problems derive fromthe interaction of teeth with bone surrounding the teeth. The quality ofthe bone adjacent teeth varies. Some bone can withstand occlusal stressbetter than other bone. Some areas of the jaw have more alveolar boneadjacent to and supporting a tooth than do other areas of the jaw.Another factor which can be utilized to determine the optimal shape anddimension of the implant (and crown) is the material used to fabricatethe implant.

An eight foot long two inch by four inch piece of lumber better resistsa force which is applied perpendicular to the length of the lumber andto a two inch side of the lumber than it resists the same force appliedto a four inch side of the lumber and perpendicular to the length of thelumber. Similarly, the orientation of an implant root with respect tothe surrounding bone can have a bearing on the ability of the root andthe implant to resist a force vector which is applied to the implant ata particular point and at a particular orientation. Therefore, theorientation of the roots of the implant is another factor which can betaken into consideration by a computer in designing the optimal implant.Still another factor is the shape and position of the tooth (or teeth)which opposes and will contact the crown on the implant after theimplant and crown are anchored in alveolar bone.

In the dental implant art, the “Theory of Available Bone” teaches thatimplants are customized to fit in existing bone. The preferred method ofthe invention directly contradicts the Theory of Available Bone becausethe method of the invention teaches optimizing the effectiveness of animplant by first defining the optimal shape and dimension and thedensity or other physical properties of the bone which should beavailable to anchor the implant. In the method of the invention, if asufficient volume of bone is not available, additional bone volume isgenerated by packing HA, HAC or some other material on existing bone togenerate new bone, by using growth factors to generate new bone, or byusing any other desired procedure to generate new bone. If the densityof the existing bone is not sufficient, existing bone can be removed andreplaced with HA, HAC, or another desired composition which will havethe desired density or other physical properties or which will cause newbone to grow which has the desired density or other physical properties.HAC can form bone consisting of about 77% by weight mineral composition.This is denser than natural bone and can be particularly desirable informing new bone in the posterior bone areas of the mouth. The bone inthe posterior areas of the mouth supports the molars. Such bonetypically is less dense than the bone in the anterior areas of themouth. Bone in the anterior areas of the mouth supports incisors. Inaddition, if the existing bone volume is too great, bone can be removed;for example, a bone spur could be removed. Consequently, the method ofthe invention propounds a “Theory of Optimal Bone—Optimal Implant”design and implementation in which existing bone structure can bealtered and the design of each implant can, if appropriate, differ fromthe design of the other implants in a patient's mouth in order to insurethat a implant is formed which effectively distributes the occlusalforces generated on the implant and bone during use of the teeth. Anydesired set of criteria or parameters can be used in defining thedesired volume, density, and other physical properties of the bone usedto support an implant. For example, but not by way of limitation, thevolume of bone typically will approximate the volume of the originalbone structure which is (or was) present in the mouth when the patientis a young adult. Such bone volume is readily measured or, in the eventportions of the original bone structure have been lost, can be readilyapproximated. The desired density of the bone typically presently willbe at least equal to the density of the original bone structure.Further, by way of example, the largest possible bite force is notnecessarily produced in a direction which is perpendicular to theocclusal plane. The posteriorly and medially directed forces generallyreach higher values than the anteriorly and laterally directed forces,respectively.

A computer can also be utilized to determine the position of the implantat which the implant optimally distributes stresses into surroundingbone. The optimal position of the implant can be determined based uponselected factors included, but not limited to, the morphology of thesurrounding alveolar bone, the size and stability of adjacent teeth,etc. For example, once the shape and dimension of an implant isdetermined, the implant may better distribute stress if it is positionedin (or on) alveolar bone closer to a first adjacent tooth than to asecond adjacent tooth because the quality of bone is better near thefirst adjacent tooth.

The shape and dimension of the crown can depend on factors including,but not limited to, the type of tooth (a molar has more cusps than anincisor), the size of the space in the patient's mouth in which thecrown must fit, and the material used to fabricate the crown (a strongermaterial might enable portions of the crown to be smaller than if aweaker material is used).

After the shape and dimension of the implant and crown are defined, theimplant and crown can be manufactured using computerized equipment. Acomputerized lathe system could, for example, be used to cut the implantfrom a piece of metal and to cut, mold, or otherwise form the crownwhich is secured to the implant. Or, the implant and crown can beproduced utilizing any desired conventional production methods. Afterthe implant and crown are produced, the implant is anchored at thedesired position in the alveolar bone using any of the proceduresearlier described. For example, on opening can be formed in the alveolarbone, the implant inserted in the opening, and HA or other materialpacked around the implant to anchor the implant in the opening. Thecrown can be attached to the implant before or after the implant issecured in the alveolar bone.

Locating an implant in the upper molar area of the mouth can bedifficult because the alveolar crestal bone is thin and adjacent thesinuses. Consequently, the mass or volume of available bone in which toanchor an implant is marginal. In order to position an implant in thealveolar crestal bone in the upper jaw, a first prior art procedure wasdeveloped. In this first prior art procedure, the alveolar bone isscored along a rectangular line. The portion of the alveolar bonecircumscribed by the score line, referred to herein as the “pad”, isthen carefully pushed inwardly to avoid tearing the Schneiderianmembrane and to form a rectangular opening through the alveolar bone. Ablock-shaped base is inserted through the rectangular opening in thealveolar bone to a position in which the base contacts or is adjacentthe pad. The area around the base is filled with loose hydroxyapatitematerial and the opening in the alveolar bone is covered with the gum oranother material to permit the hydroxyapatite to harden. Six to ninemonths later, the gum is reopened to anchor an implant and/or artificialcrown in the block-shaped base.

The foregoing first prior art procedure for positioning an implant inthe molar alveolar bone has several disadvantages. First, avoidingrupture of the Schneiderian membrane is sometimes difficult, which meansthere is an increased risk that infection in the patient's sinus willspread into the hydroxyapatite or other areas of the graft. Second, theblock-shaped base must be covered, or buried, while the hydroxyapatitehardens. This means a second later operation is required to insert anartificial crown or implant in the base once the hydroxyapatite hardens.Third, the insertion of an implant is postponed for six to nine monthswhile the sinus graft heals. Fourth, the block-shaped base tends toshift out of its desired position adjacent the pad, which makes itdifficult, if not impossible, to properly position the implant when thegum is later reopened and the implant is inserted in the block-shapedbase.

A second prior art procedure, termed the lateral sinus lift procedure,was developed to overcome shortcomings in the first procedure discussedabove. In this second prior art procedure, a cut is made through themaxilla, exercising care not to rupture the Schneiderian membrane. Thecut forms a flap which is displaced, or lifted, laterally and upwardlyinto the sinus cavity, again without rupturing the Schneiderian membranewhich lines the sinus cavity. Avoidance of damage to the Schneiderianmembrane during the lateral sinus lift is important because rupture ofthe membrane permits the rapid spread of infection in the sinus cavity.In the event the Schneiderian membrane is ruptured, a resorbablecollagen pad is used to cover the rupture, or the rupture is otherwiserepaired. After the flap is lifted, the space intermediate the flap andthe alveolar crest is filled with porous bydroxyapatite. Six monthslater, an opening, i.e., an osteotomy, is carefully drilled through thealveolar crest and into the hardened hydroxyapatite. The opening closelyconforms to the shape and dimension of an implant which is fitted intothe opening.

The foregoing second prior art procedure for positioning an implant inthe molar alveolar bone has several disadvantages. First, avoidingrupture of the Schneiderian membrane is sometimes difficult, which meansthere is an increased risk that infection from the sinus will spreadinto the graft. Second, the incision through which the hydroxyapatite isinserted must be sealed. Third, the insertion of an implant is postponedfor six months while the sinus graft heals. This means a secondoperation is required to insert the implant. Fourth, the insertion ofthe implant requires the formation of an opening which closely conformsto the shape and dimension of the implant.

A third prior art procedure for positioning an implant adjacent thesinuses is similar to the second prior art procedure described above inthat a lateral sinus lift is also performed. However, in the third priorart procedure, after the lateral sinus lift is performed an opening iscarefully drilled through the alveolar crest. This opening conforms toand receives the upper portion of an implant. Since the alveolar crestis thin, the lower portion of the implant extends from the alveolarcrest into the space intermediate the alveolar crest and the flap ofbone bent inwardly during the lateral sinus lift.

Hydroxyapatite is then packed between the alveolar crest and the flap ofbone and is packed around the implant.

The foregoing third prior art procedure for positioning an implant inthe molar alveolar bone has several disadvantages. First, avoidingrupture of the Schneiderian membrane is sometimes difficult, which meansthere is an increased risk that infection will travel from the sinusinto the graft. Second, gum tissue must be used to cover, or bury, theimplant while the hydroxyapatite solidifies. This necessitates a lateroperation to expose the implant to attach an artificial crown to theimplant. Third, the insertion of the artificial crown in the implant ispostponed for six months while the sinus graft heals. Fourth, theinsertion of the implant requires the formation of an opening whichclosely conforms to the shape and dimension of the implant.

One method of the implant of the invention facilitates the insertion ofan implant in the alveolar crest adjacent the atrophic posteriormaxilla. This method of the invention is illustrated in FIGS. 19 to 21.In FIG. 19, a retractor 114 is utilized to draw soft tissue away fromthe posterior maxilla 111. A drill or other tool is used to cut throughthe maxilla 111 to form a rectangular groove 130 defining a flap 112. Ifnecessary, the maxilla 111 can be scored along line 131 to facilitatethe inward and upward bending of flap 112 into sinus cavity 121 to theposition illustrated FIG. 20. An opening 132 is formed through thealveolar bone 117. An implant 119 is inserted through opening 132 intothe area intermediate flap 112 and the alveolar bone 117. Hydroxyapatitecement (HAC) 120 is used to pack around implant 119 intermediate flap112 and bone 117. The HAC is inserted through opening 132 or through theopening formed in the maxilla when flap 112 is bent upwardly andinwardly into the sinus cavity 121. If desired, the Schneiderianmembrane can be scraped away from and off of the bone to facilitatebonding of the HAC with the bone. The HAC has a putty like consistencyand rapidly sets up and hardens, typically within 10 to 15 minutes. Whenthe HAC hardens, it seals the sinus cavity 121. Sealing the sinus cavity121 is critical because bacteria in the sinus cavity 121 which mayinvade the graft through a breach in the Schneiderian membrane aresealed in the sinus cavity. Consequently, the method of the inventionpermits the Schneiderian membrane to be cut through, enables an implantto be quickly placed adjacent the maxilla, and does not require theformation through the alveolar bone (or hardened HAC) of an openingwhich closely conforms to the implant being utilized. The orientation ofimplant 119 can, until HAC 120 hardens, be adjusted by canting ortilting implant 119 in opening 132 and in the area intermediate flap 112and bone 117. HAC is presently preferred in the practice of this methodof the invention because it includes hydroxyapatite and because itrapidly sets up. Any other desirable packing material can, however, beutilized in place of HAC. Various other packing materials are discussedearlier herein.

The method of the invention may enable an implant and crown to becompletely installed in one operation. In contrast to the prior artprocedures described above, the method of the invention does not requirethat an initial incision be made, be closed, and then be reopened at alater date to complete the implant procedure in the method of theinvention, the implant and/or artificial crown attached to the implantcan extend through the gum into the mouth soon after an opening isformed through alveolar bone and after the Schneiderian membrane isruptured.

The method illustrated in FIGS. 19 to 21 can also be carried out withoutforming flap. 112. In this procedure, opening 132 through the alveolarbone 118 is formed and HAC putty is packed between the maxilla 111 andother bone 133 bounding the sinus cavity 121. The implant 119 ispositioned in the HAC. If desired, the entire sinus cavity 121 can befilled with HAC or another packing material. Again, if desired, theimplant and/or artificial crown attached to the implant can extendthrough the gum into the mouth.

In another embodiment of the invention, genetically produced livingmaterial is used to form an implant in the bone of a patient. The DNAstructure of a patient is analyzed from a sample of blood or othermaterial extracted from a patient and a biocompatible tooth bud 122(FIG. 3) is produced. The bud 122 is placed in an opening 123 in thealveolar bone and packing material is placed around or on top of the bud122. The size of opening 123 can vary as desired. The packing around bud122 can comprise HAC 124, hydroxyapatite, blood, growth factors, or anyother desirable packing material. The bud 122 grows into a full growntooth in the same manner that tooth buds which are in the jaws ofchildren beneath baby teeth grow into full sized teeth. In a firstvariation of this embodiment of the invention, analysis of the DNA ofthe patient is used to identify and select in vitro the genetic materialwhich causes the creation and growth of a tooth bud. This geneticmaterial at least includes a gene or genes, and may include otherportions of the DNA. A transcriptional activator is utilized to activatetranscription of these tooth bud genes in vitro. An enhancer is used todrive the specific expression of the transcriptional activator. Afterthe enhancer drives the expression of the transcriptional activator, thetranscriptional activator transactivates the tooth bud genes. Nutrientsand/or other growth factors can be used to sustain and/or promote thecreation and growth of, or if appropriate, to cause the differentiationof, a tooth bud after the tooth bud genes are activated. After the toothbud reaches a desired size, it is transplanted into the jaw bone of apatient. As used herein, the term tooth bud designates a partially growntooth. Nutrients and/or other growth factors can be used to sustain andpromote the growth of, or if appropriate, to cause the differentiationof, the tooth bud after it is transplanted into the jaw of a patient.Instead of tooth bud genes, genes which cause the morphogenesis andfurther growth of other organs or hard or soft tissue in the body can beidentified from the patient's DNA and utilized to grow in vitro organsor tissue for transplant into the body. The organs or tissue can bepartially or completely grown at the time of transplant in a secondvariation of the above embodiment of the invention, the structure of thegene or genes which control the growth of a tooth bud in a human beingis known, and the genetic material comprises comparable artificiallyproduced genes, or genes harvested from other human beings or animalsare transactivated to create and grow a tooth bud. Such artificiallyproduced genes or genes from other animals are transactivated to createand grow a tooth bud in vitro, after which the bud (or other organ ortissue) is transplanted into the body of the patient. The tooth budgrows in a tooth which is comprised of dense, semirigid, porous,calcified skeletal tissue.

In another embodiment of the invention, instead of transplanting a bud122 into the jaw of a patient, a quantity of genetically produced livingmaterial which causes bud 122 to form in the alveolar bone can be placedat a desired position in the alveolar bone such that bud 122 ismorphogenetically created in vivo and grows into a full sized tooth.Instead of forming an opening 123, a needle or other means can be usedto simply inject the genetically produced living material into aselected location in the alveolar bone.

As would be appreciated by those skilled in the art, geneticallyproduced materials can be inserted in the body to cause the body togrow, reproduce, and replace leg bone, facial bone, and any otherdesired soft and hard tissue in the body. In one variation of thisembodiment of the invention, the genetic material is placed at a desiredposition in the alveolar bone (by, for example but not by way oflimitation, forming an opening 123 to receive the genes or by utilizinga needle to insert the genes at a desired site) to create and growmorphogenetically a tooth bud and, subsequently, a tooth. The geneticmaterial is presently preferably accompanied by a transcriptionalactivator to turn on the genes' expression, an enhancer to drive thespecific expression of the transcriptional activator, and by nutrientsand/or other growth factors which promote the in vivo creation andgrowth of a tooth bud and tooth. The genes can be transcriptionallyactivated either prior to being inserted or after insertion in thealveolar bone. Instead of tooth bud genes, genes which cause themorphogenetic creation and growth of other organs or other hard or softtissue in vivo can be identified from the patient's DNA or from anothersource, and the genetic material can comprise comparable artificiallyproduced genes or genes removed from another animal or otherwisegenerated. The genetic material is then inserted at desired locations ina patient's body and utilized to create and grow morphogenetically invivo organs or other hard or soft tissue. Such genes presentlypreferably are accompanied by a transcriptional activator to turn on thegene's expression, an enhancer to drive the specific expression of thetranscriptional activator, and by nutrients and/or other growth factorswhich promote the creation and growth of a tooth bud and tooth. Thegenes can be transcriptionally activated prior to or after they areinserted in a patient's body. Any desired substance or means can, aswould be appreciated by those of skill in the art, be utilized to causethe activation or initiation of a gene or genes to express themselves bycreating and growing morphogenetically an organ or other hard or softtissue at a desired location or location(s) in the body of a patient.

The gene or genes used to create and grow morphogenetically a particularorgan or other tissue in vivo or in vitro can, if desired andappropriate, be accompanied by or be connected to other genes-or DNAmaterial which does not play a part in the growth of the desired organor other tissue.

In another embodiment of the invention, I provide a method for curingdental disease. The method comprises the step of introducing into thebody a substance or form of energy which replaces or alters a gene orgenes in the patient's DNA to improve the ability of the patient's todefend against, weaken, or destroy bacteria or viruses which causedental disease. The replaced or altered genes express themselves in atleast some of new cells subsequently produced by the patient's body. Forexample, the altered or new genes in the patient's DNA may make it moredifficult for bacteria, cytokines, or bacterial antigens to penetratethe gum tissue in the mouth of a patient. The particular embodiment ofthe invention which is preferred is using a chemical substance, heat,electromagnetic energy, or any other means to alter the structure of anexisting gene or genes in the patient's DNA or the bacteria's or virus'DNA in vivo, i.e. alters the DNA while the DNA is in the patient's body.This embodiment can be used to improve the body's capability to defendagainst any disease or illness and is different from current prior artmethods of importing new genes which are intended to replace orsupersede the original genes existing in the patient's DNA.Morphogenesis or morphogenetics is the origin and evolution ofmorphological characters and is the growth and differentiation of cellsand tissues during development.

The HAC 120, 124 or other packing material used in the implant methodsof the invention can include BIODEL or other small polymer beads orcarriers of antibiotic materials.

As used herein, hydroxyapatite cement (RAC) is a cement composedentirely or in substantial part of calcium phosphate salts. HAC can becombined with water to form a dense paste which is applied and shapedintraoperatively. HAC sets in vivo in approximately 10 to 15 minutes toform a structurally stable implant composed of microporoushydroxyapatite. The calcium phosphate salts tetracalcium phosphate andanhydrous dicalcium phosphate are the primary components of HAC. Thesesalts react in water to isothermically form hydroxyapatite. After thecalcium phosphate salts in powder form are mixed with water, theresulting composition sets in about ten to fifteen minutes. Themicroenvironment in the set cement is saturated with calcium phosphatesalts. Hydroxyapatite precipitates in situ from this microenvironmentduring a reaction which typically takes from four to six hours.

A further embodiment of the invention concerns the integration of adental implant into the lower jaw of a patient. Portions of the bonecomprising the lower jaw are hollow and lined with marrow or other softtissue. A first small opening 134 (FIG. 3) can be formed through theoutside of the jaw and a second small vent opening can be formed throughthe inside of the jaw or elsewhere. A pressurized tube or other means isused to inject hydroxyapatite cement slurry through opening 134 into thehollow area in the lower jaw. The second opening serves as a vent whichpermits air or other material to escape from within the lower jaw whenhydroxyapatite cement slurry is injected in the jaw. If desired, thefirst opening can be made slightly larger than the tube used to injectHAC slurry into the jaw such that the first opening permits air or othermaterial in side the jaw to vent outwardly through the first openingwhile HAC slurry flows from the tube into the jaw. In this case, thesecond vent opening may not be required. An X-ray(s) can be taken of thejaw to insure that the desired areas of the lower jaw are filled withHAC slurry.

After the HAC slurry is injected into the jaw, the first and secondopenings are plugged with HAC putty, polyglycolic acid, bone wax, oranother desirable material. After the HAC slurry which was injected intothe jaw hardens sufficiently, on opening can be made through thealveolar bone of the lower jaw and into the hardened HAC to receive animplant.

A HAC slurry injection method similar to the slurry injection methoddescribed above for the lower jaw can be used to inject HAC slurry intoa space between the sinuses and alveolar bone of the upper jaw. A smallaccess opening is drilled through the maxilla. Or, the Caldwell-Lucapproach can be utilized to gain access to the sinus through the nose.Once access is gained to the sinus, an instrument is used to score andrupture the sinus membrane so that HAC injected into the sinus cancontact and bond to the underlying bone. HAC slurry or another desirablematerial is then injected into the sinus through the opening with a tubeor by using other means. After the HAC slurry hardens, an opening can beformed through the alveolar bone and into the hardened HAC to receive animplant. HAC slurry, injectible hydroxyapatite, or other desiredmaterials—including but not limited to bioactive osteogenicmaterials—which facilitate the formation of new hard bone by the body,can similarly be injected into the “hollow” soft tissue inner marrowareas of the femur or other bones of the body through small holes formedin the bones.

Genes express themselves by creating and growing morphogenetically anyorgan or other hard or soft tissue. Transcriptional activators turn on agene's expression.

Transcription is the synthesis of messenger RNA (mRNA), the first stepin relaying the information contained in DNA. Transcription begins asthe interaction between a strand of DNA and the enzyme RNA polymerase.Enzymes can be growth factors. Various enzymes can be utilized in thesynthesis of peptides which contain amino acids that controlthree-dimensional protein structure and growth.

In accordance with the invention, genetic material plus growth factor(s)are implanted directly or indirectly to grow, reproduce, and replacedesired soft and hard tissue in the body.

The first step in making an implant is to analyze the DNA. DNA arrays(biochips) and other DNA sequencing methods are known in the art. Thegenetic material can includes a gene or genes and/or other portions ofDNA. A transcriptional activator is utilized to activate transcription.The genetic material can be from the patient, can be artificiallyproduced, or can come from other human beings or animals.

Genetic material is well conserved in nature. The Drosophila eyelessgene (ey), the mouse small ey gene (pax-6), and the Aniridia gene inhumans are all homologous.

Transgenic animals have attached a promoter (a growth factor) to aspecific gene. The resultant initiation of transcription produces adesired protein. For example, human growth hormone can be produced by afarm animal. Promoters are tissue specific. To produce the proteinalbumin, the gene for albumin is attached to a promoter that is foundonly in liver tissue. Once the albumin producing promoter—gene pair isinserted into the genome, albumin is produced by future generations.

The initiation of transcription in the fly Drosophila is caused by atranscriptional activator which is obtained from yeast and is calledGAL4. GAL4 causes tissue specific expression in flies. An upstream genefor eye formation in a fly is ey (eyeless). A growth factor is attachedto the ey gene to grow an eye. Two sets of flies are mated to produce ageneration of flies having additional eyes.

The first set of flies is genetically engineered to randomly insert GAL4into its genome at twenty different locations.

The second set of flies is also genetically manipulated by placing inthe eggs of the second set of flies the recombinant eyeless gene andGAL4 binding sites. The eggs mature to produce flies each having theeyeless gene in every cell in the flies body.

Genomic engineering of all kinds has created an infinite range ofgenetic possibilities for implants and growth factors due to DNA cloningand recombinant DNA. Cis position and trans position genes are possible.In additional, annealing techniques allow DNA with DNA, RNA with RNA, orDNA with RNA. Polymerases catalyze the combining of nucleotides to formRNA or DNA. Transcription factors are DNA-binding proteins that controlgene activity. Translation is the second step in the relay of geneticinformation. During translation, the sequence of triplets in mRNA istranslated into a corresponding sequence of amino acids to form apolypeptide as the gene product. Termination codons signal the end oftranslation.

Antisense RNA (or DNA), cDNA's, and expression vector can be geneticallymanipulated or produced. The term DNA as used herein also includesmitochondrial DNA.

Genomic manipulation can also be based on locating, isolating,attaching, and manipulating single molecules. For example, the processof transcription (as seen through atomic force microscopes) has beenhalted by the removal of a single nucleoside triphosphate (NTP) that theRNA molecule needed for transcription. Thus, the atomic and subatomiclevels are important in genetic engineering.

Genetic engineering can create implants and growth factors which behavein desired manners and produce selected desired results and pathways. Asused herein, genetic engineering can create materials that are able tocontrol the flow of matter and/or energy in a deliberate way by spatial,temporal, physicochemical or other physical means alone or incombination.

Desired tissues and organs can also be produced by the process ofnucleation.

Genes control structure and function. A gene or a bit of geneticmaterial may act as a master control gene which activates thousands ofother genes to construct a living organ. Each one of two or moredifferent genes can produce the same organ: For example, in Drosophila,the ey gene and the toy gene both are capable of eye formation.

Since genomic engineering can create a myriad of genetic possibilities,a pathway description of cellular interactions, intracellular andextracellular matrix combinations, and mitogenic or morphogenic stagesis impractical.

Complex tissues and organ systems are formed through cellularproliferation and differentiation. This orderly process is regulated bypeptide growth factors which are secreted locally and mediate cellularevents by triggering cell surface receptors on their target cell(s).

Cells stick together, viruses stick to cells, and white blood cellsstick to invading organisms. Optical tweezers developed at Bell Labs inthe 1980 's can measure and evaluate the “stickiness” of cells andviruses. Sticky cells can be used to attach genetic implants to selectedsites. This is, for example, important when placing a soft tissueimplant in or on a site of an artery wall. In this manner, an additionalheart could be grown from a genetic implant. Once matured to areasonable state, this new heart can be the body's primary heart and theold heart can be evacuated surgically. Any venous or arterialconnections, reconfigurations, or ligations can be surgically attendedto. Any other organ can be similarly produced at any desired site insoft or hard tissue.

Genetic implant can form a single pre cursor area and later split intwo. For example, the ET gene causes two eyes to form from a singleregion.

Multifactorial and nonspecific cells (such as stem cells and germinalcells) can provide the necessary in vivo and in vitro cascade of geneticmaterial once an implanted master control gene's transcription has beenactivated. Likewise, any host cell, cloned cell, cultured cell, or cellwould work. Genetic switches (such as the insect hormone ecdysone) canbe used to control genes inserted into humans and animals. These geneswitches can also be used in cultured cells or other cells. Geneswitches govern whether a gene is on or off making possible precise timeof gene activity.

Cellular products and their derivatives can be growth factors. Viralvectors can carry and insert new genes into chromosomes. Growth factorscan positively or negatively control genetic transcription. Snippets ofDNA with characteristic DNA fingerprints can be used as implantmaterials. Transcription factor binding sites as well as receptor sitescan be genetically engineered and utilized as needed. Receptor sites canalso be in the nucleus of cells.

Genetic implant preferably integrate biologically into the hostenvironment.

Murine and human genomes (and perhaps the entire metazoa) areconsiderably conserved at the nucleic acid and gene linkage levels.

In early tooth germ, bone morphogenic proteins BMP-2 and MPB-4 regulateexpression of the homeobox containing genes MSX-1 and MSX-2. Thesegenes, along with the eyeless gene in Drosophila may be consideredupstream genes.

The homeobox containing gene MHox regulates the epithelial-mesenchymalinteractions required for skeletal organogenesis. The paired-likehomeobox gene MHox is required for early events of skeletogenesis inmultiple lineages.

The homeobox gene controlling the growth of kidneys has been identified.

Organs, a join capsule, a ligament, or a ligament with an organ attachedcan be grown at any hard or soft tissue site.

Genes express themselves by creating and growing morphogenetically anyorgan or other hard or soft tissue. Transcriptional activators turn on agene's expression.

Genes may also play important roles in mechanisms that control thedifferentiation of structures within and between organs duringorganogenesis.

Gap junction proteins permit the exchange of regulatory moleculesbetween cells and play important roles during organogenesis.

EXAMPLE 1

MSX-1 and MSX-2 are the homeobox genes that control the generation andgrowth of a tooth. A sample of skin tissue is removed from the patientand the MSX-1 and MXS-2 homeobox gene(s) are removed from skin tissuecells. The genes are stored in an appropriate culture medium.

Germinal cells in the process of transcription are obtained from thepatient by biopsy or surgical excision. The germinal cells are in hardbone tissue adjacent the apex of the immature forming root of apatient's tooth. These cells are selected because they are activelytranscribing root structure and contain active growth and transcriptionfactors which facilitate the formation of the tooth germ. The germinalcells are placed in an appropriate nutrient culture medium outside thepatient's body. The homeobox genes MSX-1 and MSX-2 are added to thenutrient culture with the germinal cells. The nutrient culture ismaintained at an optimum temperature, which is presently preferably 98.6degrees F., but can be varied as desired. The homeobox genes MSX-1 andMSX-2 are permitted to bind with transcription factors in germinalcells. After the genes bind with transcription factors, the germinalcells and bound genes are replanted in the patient's body at the toothsite from which the germinal cells were harvested.

EXAMPLE 2

Example 1 is repeated, except that the homeobox genes are provided witha genetically engineered binding site for attaching to the receptor siteon the transcription factor. Similar results are obtained.

EXAMPLE 3

Example 1 is repeated, except that the germinal cells are obtained fromsoft periodontal ligament tissue immediately adjacent the apex of theimmature forming root of a patient's tooth. These cells are selectedbecause they are actively transcribing root structure and contain activegrowth and transcription factors which facilitate the formation of thetooth germ.

EXAMPLE 4

Example 1 is repeated, except that the homeobox genes are provided witha genetically engineered binding site for attaching to the receptor siteon the transcription factor. Similar results are obtained.

EXAMPLE 5

MSX-1 and MSX-2 are the homeobox genes that control the generation andgrowth of a tooth. A sample of skin tissue is removed from the patientand the MSX-1 and MXS-2 homeobox gene(s) are removed from skin tissuecells. A tooth is removed from the mouth of a patient. The tooth thatwas removed had an immature root structure. Transcription was occurringat the apex of the tooth that was removed. The homeobox genes MSX-1 andMSX-2 are placed at the apex of socket immediately following theextracting of the tooth. The genes bind with the transcription factor(s)and express themselves to begin the genetic cascade to form early toothgerm. The patient's body completes the formation of the tooth.

EXAMPLE 6

Example 5 is repeated, except that the homeobox genes are provided witha genetically engineered binding site for attaching to the receptor siteon the transcription factor. Similar results are obtained.

EXAMPLE 7

Example 5 is repeated, except that prior to insertion of the homeoboxgenes in the tooth socket, tissue on the bottom of the tooth socket isloosened to expose bone cells.

EXAMPLE 8

Example 5 is repeated, except that after the tooth is pulled, add atranscription factor and energy to activate genes to initiate theformation of tooth germ.

EXAMPLE 9

Example 8 is repeated, and the transcription factor and energy activatethe MSX-1 and MSX-2 genes.

EXAMPLE 10

Example 1 is repeated, except that BMP-2 and BMP-4 growth factors areobtained by recombinant or natural extraction from bone.

EXAMPLE 11

MSX-1 and MSX-2 are the homeobox genes that control the generation andgrowth of a tooth. A sample of skin tissue is removed from the patientand the MSX-1 and MXS-2 homeobox gene(s) are removed from skin tissuecells. The genes are stored in an appropriate nutrient culture medium.

BMP-2 and BMP-4 growth factors are obtained by recombinant or naturalextraction from bone.

Living stem cells are harvested from the bone marrow, the blood of thepatient, or from cell culture techniques. The stem cells are placed in anutrient culture medium at 98.6 degrees. The temperature of the culturemedium can be varied as desired but ordinarily is between 40 to 102degrees F.

MXS-1 and MXS-2 transcription factors are obtained which will initiatethe expression of the MXS-1 and MXS-2 homeobox genes.

The MXS-1 and MXS-2 transcription factors, BMP-2 and BMP-4 bonemorphogenic proteins, and MXS-1 and MXS-2 genes are added to thenutrient culture medium along with the living stem cells.

EXAMPLE 12

Example 11 is repeated except that the transcription factors bind to areceptor complex in the stem cell nucleus.

EXAMPLE 13

Example 11 is repeated except that the MXS-1 and MXS-2 transcriptionfactors are not utilized. The transcription of the MXS-1 and MXS-2homeobox genes is activated by applying an electric spark to thenutrient culture medium.

EXAMPLE 14

Example 13 is repeated except that the stem cells are starved and thetranscription of the MXS-1 and MXS-2 homeobox genes is activated byapplying an electric spark to the nutrient culture medium.

EXAMPLE 15

WT-1 and PAX genes are obtained from a sample of skin tissue is removedfrom the patient. The genes are stored in an appropriate nutrientculture medium. PAX genes produce PAX-2 and other transcription factors.

BMP-7 and other kidney related BMP growth factors are obtained byrecombinant or natural extraction from bone.

Living stem cells are harvested from the bone marrow, the blood of thepatient, or from cell culture techniques. The stem cells are placed in anutrient culture medium at 98.6 degrees. The temperature of the culturemedium can be varied as desired but ordinarily is between 40 to 102degrees F.

The WT-1 and PAX genes, and BMP-7 and other kidney BMPS are added to thenutrient culture medium along with the living stem cells.

A primitive kidney germ is produced. The kidney germ is transplanted inthe patient's body near a large artery. As the kidney grows, its bloodsupply will be derived from the artery.

EXAMPLE 16

The Aniridia gene is obtained from a sample of skin tissue is removedfrom the patient. The gene(s) is stored in an appropriate nutrientculture medium.

Aniridia transcription factor (activates expression of the Aniridiagene) and growth factors (function to help stem cells differentiateduring morphogenesis to form an eye) are obtained.

Living stem cells are harvested from the bone marrow, the blood of thepatient, or from cell culture techniques. The stem cells are placed in anutrient culture medium at 98.6 degrees. The temperature of the culturemedium can be varied as desired but ordinarily is between 40 to 102degrees F.

The Aniridia transcription factor and growth factors and the Aniridiagene are added to the nutrient culture medium along with the living stemcells.

A primitive eye germ is produced. The kidney germ is transplanted in thepatient's body near the optic nerve. As the kidney grows, its bloodsupply will be derived from nearby arteries.

EXAMPLE 17

The Aniridia gene is obtained from a sample of skin tissue is removedfrom the patient. The gene(s) is stored in an appropriate nutrientculture medium.

Aniridia transcription factor (activates expression of the Aniridiagene) and growth factors (function to help stem cells differentiateduring morphogenesis to form an eye) are obtained and added to thenutrient culture medium.

An eye germ develops. A branch of the nearby maxillary artery istranslocated to a position adjacent the eye germ to promote thedevelopment of the eye germ. The eye germ matures into an eye whichreceives its blood supply from the maxillary artery.

The term “cell nutrient culture” as used herein can include any or anycombination of the following: the extracellular matrix; conventionalcell culture nutrients; and/or, a cell nutrient such as a vitamin. Assuch, the cell nutrient culture can be two-dimensional, threedimensional, or simply a nutrient, and is useful in promoting theprocesses of cellular dedifferentiation, redifferentiation,differentiation, growth, and development.

As used herein, the term “physiological nutrient culture” is a selectedmedia(s) to control and direct an event(s) in living host system(s)(e.g., cardiovascular, pulmonary, musculoskeletal, etc.), organ(s),tissue(s), cell(s). A media is a fluid solution, gel, or quasi-solidsoultion (mechanical mixture) which supports and directs normaldevelopmental pathways for cell and cell products. An event is one ofthe sequence of growth, division, cellular aggregation, development ofcellular form, development of aggregate cellular form, secretions, etc.which lead to the development of an organ. A physiological nutrientculture can affect macromolecule(s), molecule(s), atom(s), and subatomicparticle(s) in said living things. A physiolocial nutrient culture caninclude macromolecule(s), molecule(s), atom(s), and subastomicparticle(s). A cell nutrient culture is a physiological nutrientculture. A physiological nutrient culture is not necessarily a cellnutrient culture. A physiological nutrient culture promotes cellularsurvival and cellular proliferation in a desired form(s) or function(s),and promotes differentiation to a selected specific function.

Growth factors control cell growth, division, differentiation,migration, structure, function, and self-assembly. Growth factorsinclude chemical regulators and structural/mechanical regulators. Growthfactors, particularly when mimicking the extracellular matrix, exertgeometric and nongeometric physical, mechanical, chemical, electrical,and/or structural forces on a cell. They can change a cell's content,shape, form, and/or function. In essence, they can have a kaleidoscopiceffect which is very useful in creating and promoting the growth andmorphogenesis of irregularly structured cells, tissues, or complextissues and organs such as neurons, nervous tissue, or the brain. Thesegrowth factors can activate and regulate genetic transcription.

The invention utilizes the body as an organ/tissue factory. There may,however, be occasions where the organ/tissue is completely grown ex-vivobefore replant or transplant.

Physical examinations can be done on any patient to ascertainapplications of the inventions herein described.

Genetic manipulation to any portion of a gene, gene(s) protein, growthfactor, or cell(s) whether taken from the patient or from any othersource can be done to improve organ or tissue longevity, function, orany other attribute. These materials may be synthesized in any fashion.

The extracellular matrix (ECM) may constantly change as a result ofmechanical, endocrine, or genetic factors.

A nutrient package's wall thickness can be two or less nanometers, or itcan be any other thickness desired. Its wall can be fabricated fromprotein or from any other biological or synthetic material desired.

An organ, as used herein, consists of two or more kinds of tissuesjoined into one structure that has a certain task. For example, theheart is an organ who job is to circulate blood throughout the body. Theheart is made up of connective tissue, muscle tissue, and nervoustissue. Organ systems comprise groups of organs. A major activity in thebody is performed by each organ system. For example, the digestivesystem comprises organs that enable the body to use food. Likewise, thenervous system includes organs that carry signals from one area of thebody to another.

Genetic material comprising a portion of a gene, a gene, genes, a geneproduct (i.e., a composition a gene causes to be produced like, forexample, an organ-producing growth factor), growth factor, or an ECM(extracellular matrix) can be used in or on the body to grow an organ ortissue. For example, the vascular epithelial growth factor gene (VEGF)or its growth factor equivalent can be inserted into the body to causean artery to grow. When insertion of a gene, portion of a gene, geneproduct, growth factor, or ECM in vivo or ex vivo is referred to hereinin connection with any of the implant techniques of the invention, it isunderstood that a cell nutrient culture(s), physiological nutrientculture(s), carrier(s), enhancer(s), promoter(s), or any other desiredauxiliary component(s) can be inserted with the gene or at the samelocation as the gene, growth factor, ECM, etc.

An artery is an organ from the circulatory system. An artery can begrown in the heart, legs, or other areas by injecting a gene or othergenetic material into muscle at a desired site. Size, vascularity,simplicity of access, ease of exploitation and any other desired factorscan be utilized in selecting a desired site. The gene is one of severalknown VEGF genes which cause the production of vascular endothelialgrowth factors. Several VEGF genes which produce vascular endothelialgrowth factors are believed to exist because nature intends for there tobe several pathways (i.e., genes) which enable of the production ofnecessary growth factors. The existence of several pathways is believedimportant because if one of the genes is damaged or inoperative, othersimilar genes can still orchestrate the production of necessary growthfactors. VEGF genes are used by the body to promote blood-vessel growth.VEGF genes are assimilated (taken in) by muscle cells. The genes causethe muscle cells to make a VEGF protein which promotes the growth of newarteries. VEGF proteins can be made in a lab and injected into a patientintravenously, intraluminally, or intramuscularly to promote the growthof an artery. Or, the genes (or other genetic material) can be appliedwith an angioplasty balloon, with the assistance of a vector, or by anyother method.

It is not always desirable to grow a completely new organ. Sometimesgrowing a portion of an organ is desirable. For example, in some heartattacks or strokes, a portion of the heart or brain remains viable and aportion dies. An injection of a gene to form cardiac muscle and/or aninjection of a gene to form an artery can be utilized to revive orreplace the dead portion of the heart. The dead portion of the heart may(or may not) be used as a matrix while the new muscles and vessels grow.Thus, in this example, a partial new organ and is grown in apre-existing organ. A pacemaker may (or may not) be necessary. A secondinjection of a gene may (or may not) be necessary to stop cardiac musclegrowth once it is completed. Portions of organs throughout the body cansimilarly be repaired or replaced. It may be necessary to providegene(s) or growth factor(s) sequentially. For instance, one or moreblood vessels are grown by inserting an appropriate gene or othergenetic material into a selected area. Second, an appropriate gene orother genetic material is inserted in the selected area to grow a boneor other organ.

The size and shape limitation of the desired structure can come from acontainment and boundary contact inhibition phenomenon or by a chemicalinhibition.

A variation on the theme of growing a portion of an organ is as follows:a portion of a heart dies. The pericardium is utilized as a scaffold andseeded with cells and/or genes to grow new muscle, and genes (or othergenetic material) to grow new arteries. Immediately adjacent the deadcardiac muscle, onto or into the pericardium, the appropriate cells,genes, and/or growth factors (or other genetic material) are placed.Once the new muscle and blood vessels have grown, the function specifictissue can be applied to the damaged portion of the heart and paced, ifnecessary, to augment cardiac action. If the surgeon desires, the deadmuscle can be removed and the new muscle and blood vessels can besurgically rotated into the excised region and secured. This probablycan be done endoscopically. In essence, the pericardium is utilized toallow the new muscle wall to grow. The new muscle wall is thentransplanted into the damaged heart wall. This procedure utilizes thebody as a factory to grow an organ and/or tissue, after which the organand/or tissue is transplanted to a desired region. On the other hand,the new muscle wall may integrate itself into the old wall and notrequire transplantation.

It may be advantageous to grow an organ and adjacent tissue. Forexample, a severe burn victim may lose organs and tissues (skin, bloodvessels, fat, muscles, etc.). The gene(s), gene product(s), and/or ECM(or other genetic material) may be assembled utilizing any appropriatedelivery vehicle or system. By way of example, and not limitation, fourspray cans or other delivery apparatus can be utilized. First, musclegene in a spray can is applied in a light mist or layer. Then fat, bloodvessel, and finally skin gene(s) are applied, each from a separate spraycan. Or, possibly, all four components can be admixed in and appliedfrom a single spray can. Carriers, matrixes, isolating layers, and/orform or shape defining products may or may not be used by the operator.All the genes can be in the same spray can or combined with othersubstances. As can be appreciated by those skilled in the art, anymethod of inserting the gene(s), grow factors, or ECM into or onto thebody can be utilized. Nutrients, analgesics, antiseptics, moisturerestoring compositions and methods, and appropriate post-operativedressings can be utilized pursuant to operator discretion on an as-needbasis.

It may be desirable to restore a single function in a multifunctionalorgan. For example, a pancreas produces digestive enzymes and itproduces insulin in the Islets of Langerhans. A practitioner may chooseto stimulate only a desired portion. For example, inserting a gene forthe creation of more Islets of Langerhans can be utilized to selectivelyrestore an appropriate insulin production level without affecting theproduction of pancreatic digestive enzymes.

There is a mechanotransduction interplay the occurs from theextracellular matrix (ECM) to and across the cell membrane, through thecell's cytoskeleton, and, to the cell's DNA. Cellular products areproduced during this process and the process of morphogenesis is aidedby this procedure. It may be possible to rejuvenate an organ byinserting a growth factor (especially a growth factor that can mimicextracellular fluid to control cell growth, division, migration,structure, function, and self-assembly) into or around an organ that nolonger operates to optimal capacity or to a desired capacity. Forexample, in the interplay from the ECM to the DNA as described above, iffor any reason the DNA falls into disrepair, cellular fitness andfunction become altered and a disease state may occur. The organ ortissue no longer functions as well as desired. The insertion of thegrowth factor into or around the organ may rejuvenate and restore thefitness and function to this organ even though the cellular DNA remainsis disrepair. This procedure may, in some cases, allow the cell torepair, restore, change and reverse its DNA damage so that it canreplicate normally henceforth. Booster shots of the growth factor may benecessary.

Organs and/or tissues can be formed utilizing the patient's own cells.For example, a skin cell(s) is removed from the intraoral lining of acheek. The cell is genetically screened to identify DNA damage or otherstructural and/or functional problems. Any existing prior art geneticscreening technique can be utilized. Such methods can utilize lasers,DNA probes, PCR, or any other suitable device. If the cell is damaged, ahealthy undamaged cell is, if possible, identified and selected. If ahealthy cell can not be obtained, the damaged cell can be repaired byexcision, alkylation, transition or any other desired method. A growthfactor(s) is added to the cell to facilitate dedifferentiation and thenredifferentiation and morphogenesis into an organ or function specifictissue. Any machine known in the art can be used to check the geneticfitness of the organ and its stage of morphogenesis. A cell nutrientculture may or may not be utilized depending on the desired functionaloutcome (i.e., growth of an artery, of pancreatic Islet cells, of aheart, etc.) or other circumstances. Replantation can occur at anyappropriate stage of morphogenesis. The foregoing can be repeatedwithout the patient's own cells if universal donor cells such a germinalcells are utilized. Germinal cells do not require a dedifferentiation.They simply differentiate into desired tissues or organs when properlystimulated. Similarly, the DNA utilized in the foregoing procedure cancome from the patient or from any desired source.

During reimplantation one of the patient's own cells is returned to thepatient. During implantation, a cell not originally obtained from thepatient is inserted on or in the patient.

In the example above, if germinal cells (and in some cases, stem cells)are utilized a direct differentiation and morphogenesis into an organcan occur in vivo, ex vivo, or in vitro.

A variant on the above two examples involves inserting a selectedgene(s) or portion of a gene into a cell. For example, a cell isremoved, analyzed, and repaired if desired or necessary to assurequality (e.g., proper interaction to give structural (protein) orchemical (enzyme) product) and functional outcome (e.g., the productionof an organ).

A gene(s) or a portion of a gene is secured from the patient cell bysampling or is secured from any other source. The gene is inserted intothe cell. A growth factor(s) can be inserted in the cell simultaneouslywith the gene or at the time preceding or following insertion of thegene. Organ formation occurs and replantation is performed utilizing anyacceptable technique. Inserting an appropriate growth factor or othergene product in a cell may, without requiring the insertion of a gene inthe cell, trigger the process which causes the cell to grow an organ.Similarly, controlling the ECM contacting a cell can cause mRNA toselect and copy a segment of the cell's DNA. This segment of the cell'sDNA interacts with one or more components in the cell to produce agrowth factor or other gene product which triggers the growth of anorgan.

An organ or tissue can be made utilizing pellet, capsule, or othercarrier carrying a growth factor, a gene, a growth factor and a gene, orany other desired genetic material. These pellets can include ECMproducing compositions or components and can be inserted anywhere in thebody. Once inserted in the body, the carriers can be fixed or can bemovable; and, they can contain living material, nonliving material, orliving and nonliving material. As such, they can be prepackagedpharmaceutical carriers inserted to grow selected tissues and organs.The materials inside the carriers can be from the patient or from anyother source. Each carrier can be porous, resorbable, semisolid,gelatinous, or have any other desired physical attribute.

An auxiliary organ or a portion of an auxiliary organ can be grown. Forexample, a two chambered auxiliary pump for the heart can be grown. Mostheart problems occur on the left side. Augmentation and enlargement ofthe existing heart can help restore optimal function and help preventpathological enlargement of a poorly performing section of the heart.

An auxiliary organ can be grown in the body years before the anticipatedexpiration of the original organ. Genetic or other testing can predictorgan failure years in advance allowing an early diagnosis of the futurefailure of an organ.

Avascular necrosis can be corrected with the insertion of a gene(s)and/or growth factor or other genetic material in the body. For example,avascular necrosis is diagnosed near a joint space. VEGF or BMP genes,or, VEGF or BMP growth factors produced by VEFG or BMP genes,respectively, or any other desired genetic based material can beinserted to regrow blood vessels and/or bone. Auxiliary placementapparatus like fixation plates and/or screws, fixing compositions, orany other desired system can be utilized to strengthen or secure tissue.The genes and/or growth factors can be placed adjacent the auxiliaryplacement apparatus, can be placed in a composition adjacent theauxiliary placement apparatus, can be placed remote from the auxiliaryplacement apparatus, or, can be placed at any other desired location.

Cellular dedifferentiation, differentiation, redifferentiation, andmorphogenesis are directed and controlled by growth factors (or theirgenetic counterparts) controlling cell growth, migration, structure,function, and/or self-assembly. A growth actor (or gene or other geneticmaterial) can be inserted into or onto the body to grow missing limbs orbody parts. The insertion of a multifactorial and nonspecific growthactor (or gene) is required. Such a growth factor is pluripotent, senseswhat body part or other component is missing, and directs adjacent cellsto reconstruct the body part along genetically predetermined pathways.The process is not unlike the salamander regrowing a severed tail orlimb. Other growth factors may or may not be required.

The insertion of a growth factor (or its gene counterpart) in the bodycan be utilized to prevent and/or reduce inflammation. Growth factorscontrol cell migration. As such, they can be powerful cell inhibitors toprevent inflammatory cells from migrating into an area. Such anapplication has major usefulness in the treatment of arthritis or otherautoimmune or inflammatory diseases. Thus a growth factor can beinserted in the body to control cell migration or to perform otherfunctions described herein.

A rotator cuff deficiency often prevents normal sports activities.Ligament dysfunction can prevent jogging. Venous insufficiency canhinder prolonged standing or walking. Such musculoskeletal injuries ordeficiencies can be corrected by inserting a gene(s) and/or growthfactor(s) or other genetic material into the body to create new tissueand/or organs which replaces or augments existing tissue.

A hybrid organ or other structure can be fabricated genetically toinclude specific tissues which function as needed. For example, a kidneycontaining Islets of Langerhans cells can be produced. Such a kidney isuseful for a patient with diabetes mellitus and renal failure. Otherhybrid structures can be grown according to need.

Gene Trace Systems, Inc. of Menlo Park, Calif. has developed fullyautomated DNA sequencing technology that combines DNA probing,sequencing, and sizing reactions with laser-based “time of flight” massspectrometry. This technology (1) identifies the sequence of basechemicals in a DNA strand in five seconds, (2) permits genetic screeningtests that cost as little as a few dollars, and (3) is used for genediscovery and expression, genotyping, and disease diagnosis andidentification.

The Biological Microcavity Laser (TBML) analyzes blood and cell samplesin minutes. TBML (1) is a kind of “lab-on-a-chip” which utilizes tinyfingers of laser light to image cells which are placed in a smallchamber, (2) permits information concerning each cell in a cell sampleof millions to be extracted in a few minutes, (3) is a tool for studyingcell structure changes and sequencing DNA, (4) can identify the stagesof morphogenesis, and (5) is based on a laser device called a VCSEL(vertically-cavity surface-emitting laser). Cells being analyzed withTBML do not have to be killed and stained, as cells normally do fortypical laboratory analysis.

Stem cells associated with the central nervous system differentiate tomultiple fates: neurons, astrocytes, and oligodendrocytes. Thedifferentiation of these stem cells is influenced by extracellularsignals. For example, platelet-derived growth factor is known to supportneuronal differentiation. In contrast, ciliary neurotrophic factor andthyroid hormone T3 act on stem cells to generate astrocytes andoligodendrocytes.

Pax genes are key regulators during organogenesis of kidney, eye, ear,nose, limb muscle, vertebral column and brain.

The extracellular matrix (ECM) is a dense, fibrous network of proteinsand sugars forming a complex natural environment surrounding individualcells or groups of cells. Components of the matrix, including proteinssuch a laminin and fibronectin, bind to specific molecules calledintegrins on the cell surface. Through these integrins the matrix sendscells various signals that regulate what genes are active. These signalsultimately influence whether cells proliferate, specialize, migrate, oreven eliminate themselves. The ECM has the ability to command cells touse particular, tissue-specific genes. This allows the microenvironmentoutside of cells to confer tissue specificity. For example, capillaryepithelial cells roll up to form normal blood vessels only if grown onthe proper matrix molecules.

A gene corresponds to a segment of the DNA that codes for the synthesisof a single polypeptide chain. The definition of a gene product, as usedherein, is the polypeptide or ribosomal RNA coded for by a gene, i.e.,which a gene causes to be produced. A gene product can include proteins,transcription factor(s), and/or RNA. For example, VEGF is a gene, whileVEGF growth factor is a gene product.

Genes, a gene, a portion of a gene, ECM, and/or a nutrient media can beinserted into a cell or groups of cells by direct insertion (forexample, an apparatus like a micropipette), with a cell fragment (forexample, a plasmid from a bacterium), with a virus vector, liposome, byphagocytosis, with the help of pore-forming substance, electrically,chemically, or by any other desired technique of crossing the cellmembrane to reach the nucleus or any other desired site in the cell. Agene(s) can be transferred in the form of naked plasmid DNA. Forexample, an intramuscular injection can be made of plasmid DNA encodingthe secreted angiogenic growth factor such as vascular endothelialgrowth factor (VEGF).

In accordance with one embodiment of the invention, a gene, growthfactor, ECM (or other genetic material) and/or nutrient media isinserted into or onto the body at a specific location to induce andpromote the morphogenesis and growth of an organ or desired organsub-structure at that location. A desired organ sub-structure cancomprise a cell, group of cells, neuron, dermis, Islet cells, etc. Alsoin accordance with the invention, a gene or other genetic material isinserted into or onto a cell or group of cells outside the body toinduce and promote morphogenesis and growth of an organ or desiredstructure. Growth factors can also be utilized in combination with or inplace of a gene. The resulting induced organ or other structure istransplanted to a desired location in a patient's body.

Gene products can be inserted in a patient's body to produce an organ orother structure. For example, VEGF growth factor inserted in the bodyproduces an organ, i.e., an artery.

Selected ECM compositions or other environmental factors can induce themorphogenesis of organs or selected organ sub-structures. As usedherein, environmental factors include, but are not limited to,compositions which exert physical, mechanical, chemical, electrical,and/or structural forces on living cells.

Another variant of the invention inserts a gene and a growth factor at aselected location or locations in the body of a patient to grow aselected organ or structure. As exemplified by cloning technology, anenucleated ovum is a viable growth factor. Other subunits of a cell alsoqualify as growth factors. A gene and the extracellular matrix may alsobe inserted at a selected location or locations in a patient's body togrow an organ. Likewise, a growth factor and the extracellular matrixcan be inserted in a patient's body to form an organ.

EXAMPLE 18

A 36 year old Caucasian male experiences pain in his left leg. A medicalexamination reveals a damaged one inch long section of a large artery inhis left leg. The examination also reveals that this damaged section ofthe artery is nearly completely clogged with plaque and that the wall ofthe artery is weakened. The weakening in the arterial wall makesattempting to clean out the artery risky and also makes it risky toattempt to insert a stent in the artery.

Recombinant cDNA encoded to combine with a cell ribosome to produce thehuman growth factor VEGF is assembled into a eukaryotic expressionplasmid. The recombinant cDNA is from cDNA libraries prepared from HL60leukemia cells and is known to cause the growth of arteries. The plasmidis maintained at a room temperature of 76 degrees F.

The clones are placed in 1.0 milliliters of a normal saline carriersolution at a room temperature of 76 degrees F. to produce an geneticcarrier solution. The genetic carrier solution contains about 250 ug ofthe cDNA clones. A nutrient culture can, if desired, be utilized inconjunction with or in place of the saline carrier. Each clone isidentical. If desired, only a single clone can be inserted in the normalsaline carrier solution. The saline carrier solution comprises 0.09% byweight sodium chloride in water. A saline carrier solution is selectedbecause it will not ham the DNA clone.

Two sites are selected for injection of the genetic carrier solution.While the selection of sites can vary as desired, the sites are selectedat the lower end (the end nearest the left foot of the patient) of thedamaged section of the artery so that the new arterial section growncan, if necessary, be used to take the place of the damaged section ofthe artery in the event the damaged section is removed.

The first site is on the exterior wall of the artery on one side of thelower end of the damaged section of the artery. A containment system isplaced at the first site.

The second site is inside the wall of the artery on the other side ofthe lower end of the artery.

The genetic carrier solution is heated to a temperature of 98.6 degreesF. 0.25 milliliters of the genetic carrier solution is injected into thecontainment system at the first site. 0.25 milliliters of the geneticcarrier solution is injected at the second site inside the wall of theartery. Care is taken to slowly inject the genetic carrier solution toavoid entry of the solution into the artery such that blood stream willcarry away the cDNA in the solution.

After two weeks, an MRI is taken which shows the patient's leg artery.The MRI reveals new growth at the first and second sites.

After four weeks, another MRI is taken which shows the patient's legartery. The MRI shows that (1) at the first site a new artery is growingadjacent the patient's original leg artery, and (2) at the second site anew section of artery is growing integral with the original artery,i.e., at the second site the new section of artery is lengthening theoriginal artery, much like inserting a new section of hose in a gardenhose concentric with the longitudinal axis of the garden hose lengthensthe garden hose.

After about eight to twelve weeks, another MRI is taken which shows thatthe new artery growing adjacent the patient's original artery has grownto a length of about one inch and has integrated itself at each of itsends with the original artery such that blood flows through the newsection of artery. The MRI also shows that the new artery at the secondsite has grown to a length of one-half inch.

In any of the examples of the practice of the invention included herein,cell nutrient culture can be included with the gene, the growth factor,the extracellular matrix, or the environmental factors.

In any of the examples of the practice of the invention included herein,the concept of gene redundancy can be applied. For example, the Examples1 to 14 concerning a tooth list the genes MSX-1 and MSX-2. These genesdiffer by only two base pairs. Either gene alone may be sufficient. Afurther example of redundancy occurs in growth factors. Looking at theExamples 10 to 14, BMP4 or BMP2 alone may be sufficient. Redundancy canalso be utilized in connection with transcription factors, extracellularmatrices, environmental factors, cell nutrient cultures, physiologicalnutrient cultures, vectors, promotors, etc.

One embodiment of the invention inserts genetic material (gene, growthfactor, ECM, etc.) into the body to induce the formation of an organ.Similar inducing materials inserted ex vivo into or onto a living cellin an appropriate physiological nurturing environment will also inducethe growth of an organ. The VCSEL laser allows early detection in aliving cell of a morphogenic change indicating that organ formation hasbeen initiated. With properly timed transplantation, organ growthcompletes itself.

During the ex vivo application of the invention, a gene and/or growthfactor is inserted into a cell or a group of cells; an ECM orenvironmental factor(s) are placed around and in contact with a cell orgroup of cells; or, genetic material is inserted into a subunit of acell to induce organ growth. An example of a subunit of a cell is anenucleated cell or a comparable artificially produced environment. In invivo or ex vivo embodiments of the invention to induce the growth of anorgan, the genes, growth factors, or other genetic material, as well asthe environmental factors or cells utilized, can come from any desiredsource.

EXAMPLE 19

Genetically produced materials are inserted in the body to cause thebody to grow, reproduce, and replace in vivo a clogged artery in theheart. This is an example of site-specific gene expression. A plasmidexpression vector containing an enhancer/promoter is utilized to aid inthe transfer of the gene into muscle cells. The enhancer is utilized todrive the specific expression of the transcriptional activator. Afterthe enhancer drives the expression of the transcriptional activator, thetranscriptional activator transactivates the muscle/artery genes. Salineis used as a carrier. Cardiac muscle can take up naked DNA injectedintramuscularly. Injecting plasmid DNA into cardiac (or skeletal) muscleresults in expression of the transgene in cardiac myocytes for severalweeks or longer.

Readily available off-the-shelf (RAOTS) cDNA clones for recombinanthuman VEGF165, isolated from cDNA libraries prepared from HL60 leukemiacells, are assembled in a RAOTS expression plasmid utilizing 736 bp CMVpromoter/enhancer to drive VEGF expression. Other RAOTS promoters can beutilized to drive VEGF expression for longer periods of time. OtherRAOTS recombinant clones of angiogenic growth factors other than VEGFcan be utilized, for example, fibroblast growth factor family,endothelial cell growth factor, etc. Downstream from the VEGF cDNA is anSV40 polyadenylation sequence. These fragments occur in the RAOTS pUC118vector, which includes an Escherichia coli origin of replication and theBeta lactamase gene for ampicillin resistance.

The RAOTS construct is placed into a RAOTS 3 ml syringe with neutral pHphysiologic saline at room temperature (or body temperature of about 37degrees C.). The syringe has a RAOTS 27 gauge needle.

Access to the cardiac muscle is gained by open heart surgery, endoscopicsurgery, direct injection of the needle without incision, or by anyother desired means. The cardiac muscle immediately adjacent a cloggedartery is slowly injected with the RAOTS construct during a five secondtime period. Injection is slow to avoid leakage through the externalcovering of muscle cells. About 0.5 ml to 1.0 ml (milliliter) of fluidis injected containing approximately 500 ug phVEGF 165 in saline (N=18).The readily available off-the-shelf cDNA clones cause vascular growthwhich automatically integrates itself with the cardiac muscle. Anatomicevidence of collateral artery formation is observed by the 30th dayfollowing injection to the RAOTS construct. One end of the arteryintegrates itself in the heart wall to receive blood from the heart. Theother end of the artery branches into increasing smaller blood vesselsto distribute blood into the heart muscle. Once the growth of the newartery is completed, the new artery is left in place in the heart wall.Transplantation of the new artery is not required.

Blood flow through the new artery is calculated in a number of ways. Forexample, Doppler-derived flow can be determined by electromagneticflowmeters (using, for example, a Doppler Flowmeter sold by ParksMedical Electronic of Aloha, Oreg.) both in vitro and in vivo. RAOTSexternal ultrasound gives a semiquantitative analysis of arterial flow.Also, RAOTS angiograms or any other readily available commercial devicescan be utilized.

VEGF gene expression can be evaluated by readily available off-the-shelfpolymerase chain reaction (PCR) techniques.

If controls are desired, the plasmid pGSVLacZ containing a nucleartargeted Beta-galactosidase sequence coupled to the simian virus 40early promoter can be used. To evaluate efficiency, a promoter-matchedreporter plasmid, pCMV Beta (available from Clontech of Palo Alto,Calif.), which encodes Beta-galactosidase under control of CMVpromoter/enhancer can be utilized. Other RAOTS products can be utilizedif desired.

EXAMPLE 20

A patient, a forty year old African-American female in good health, hasbeen missing tooth number 24 for ten years. The space in her mouth inwhich her number 24 tooth originally resided is empty. All other teethexcept tooth number 24 are present in the patient's mouth. The patientdesires a new tooth in the empty “number 24” space in her mouth.

A full thickness mucoperiosteal flap surgery is utilized to expose thebone in the number 24 space. A slight tissue reflection into the number23 tooth and number 25 tooth areas is carried out to insure adequateworking conditions.

A Midwest Quietair handpiece (or other off-the-shelf handpiece)utilizing a #701 XXL bur (Dentsply Midwest of Des Plaines, Ill.)(a #700,#557, #558, etc. bur can be utilized if desired) is used to excavate animplant opening or site in the bone. The implant opening is placedmidway between the roots of the number 23 and number 25 teeth. Theopening ends at a depth which is about fifteen millimeters and whichapproximates the depth of the apices of the roots of the number 23 andnumber 25 teeth. Care is taken not to perforate either the buccal orlingual wall of the bone. In addition, care is taken not to perforate orinvade the periodontal ligament space of teeth numbers 23 and 25.

An interrupted drilling technique is utilized to avoid overheating thebone when the #701XXL bur is utilized to form the implant opening.During a drilling sequence, the drill is operated in five secondincrements and the handpiece is permitted to stall. Light pressure and agentle downward stroke are utilized. The bur is removed from the openingafter the handpiece is permitted to stall. This sequence is repeateduntil an implant opening having the desired depth is created. In theevent a standard off-the-shelf implant drill is utilized, the foregoingtechnique is not utilized and, instead, the manufacturer's recommendeddrilling technique is followed.

Once the implant opening is created, 0.5 ml of EDTA (ethylene diaminetetra acetic acid) is lavaged to the bottom of the implant opening orsite and allowed to set for two minutes. The EDTA solution is thenwashed off with sterile water. This removes the smear layer which formswhen the #701 XXL bur is used to form the implant opening.

0.5 cc of propylene glycol alginate solution is mixed with freeze driedMSX-1 matrix proteins. The resultant gel is backloaded into a Luhrlocksyringe through an 18 gauge needle. Once loaded, a smaller 27 gaugeneedle is be placed on the syringe to allow the need to be bent when itis inserted in the implant site in the mouth. The gel loses handlingqualities after about two hours and is therefore preferably utilizedwithin ten or fifteen minutes after being admixed.

The tip of the 27 gauge needle is placed at the bottom of the implantopening and 0.25 ml of gel is ejected into the bottom of the implantopening. The needle is slowly removed from the implant opening while, atthe same time, the syringe is operated to express additional gel to fillthe implant opening from the bottom of the opening to the coronal aspectof the bone surrounding the implant opening. Gum tissue is drawn overthe implant opening to close the opening and is sutured in place withEthicon suture.

Alginate gel begins to be absorbed by the patient's body within 48 hoursand binds MSX-1 proteins to bone in or adjacent the implant opening.Within about six (6) months, the formation of a tooth isradiographically confirmed.

EXAMPLE 21

Example 20 is repeated, except that the MSX-1 alginate matrix proteinsare omitted, and in their place at least one MSX-1 gene, a plasmid, anda promoter/enhancer are mixed with and included in the gel that isloaded into the syringe and injected into the implant opening. Similarresults are obtained.

EXAMPLE 22

Example 21 is repeated, except a 0.09% saline solution is utilized as acarrier instead of the alginate gel. Similar results are obtained.

EXAMPLE 23

Example 21 is repeated, except a MSX-2 gene is utilized in place of theMSX-1 gene. Similar results are obtained.

EXAMPLE 24

Example 22 is repeated, except a MSX-2 gene is utilized in place of theMSX-1 gene. Similar results are obtained.

EXAMPLE 25

Example 21 is repeated, except a PAX-9 gene is utilized in place of theMSX-1 gene. Similar results are obtained.

EXAMPLE 26

Example 22 is repeated, except a PAX-9 gene is utilized in place of theMSX-1 gene. Similar results are obtained.

EXAMPLE 27

Example 21 is repeated, except a PAX-9 protein is utilized in place ofthe MSX-1 gene. Similar results are obtained.

EXAMPLE 28

Example 22 is repeated, except a PAX-9 protein is utilized in place ofthe MSX-1 gene. Similar results are obtained.

EXAMPLE 29

Example 21 is repeated, except at least one MSX-2 gene is included incombination with the MSX-1 gene. Similar results are obtained.

EXAMPLE 30

Example 22 is repeated, except at least one MSX-2 gene is included incombination with the MSX-1 gene. Similar results are obtained.

EXAMPLE 31

Example 21 is repeated, except at least one MSX-2 gene is included incombination with the MSX-1 gene along with BMP2, BMP4, and BMP7 growthfactors.

Similar results are obtained.

EXAMPLE 32

Example 22 is repeated, except at least one MSX-2 gene is included incombination with the MSX-1 gene along with BMP2, BMP4, and BMP7 growthfactors. Similar results are obtained.

For the development of a tooth in accordance with the invention, anupstream initiator gene(s) and/or growth factor(s) inserted directly invivo or transplanted into the body at a very early stage ofmorphogenesis is sufficient for tooth formation. The general approachdelineated above for a tooth and an artery is appropriate for any organor organ system. When an organ is grown ex vivo other regulator and/orsignaling compositions can be utilized in addition to initiator genes(like MSX-1 ) and/or growth factors. During growth of a tooth, thegenetically produced materials noted below can be utilized: InitiationProliferation Morphogenesis Bmp2,4 Bmp2,4 Bmp4 EGF Dlx1-3 Collagens FGF8EGR1 Dlx1-3 Lef1 FGFs Lef1 Msx1 Lef1 Msx1 Msx2 Msx1 Msx2 Shh Msx2Notch1-3 Notch1-3 Pax9 Pax9 RAR RAR (alpha, beta RXR omega) RXR (alpha,beta Tuftelin omega) Syndecan Tenascin TGF-beta s

In the Islets of Langerhans, the initiators are: Pax-6, Pax4, ISL-1,NKX6A. Other factors are the TGF family, Gastrin, IDX-1, PDX-1, INGAP,NeuroD, HNF3beta, IPF-1, helix-loop-helix protein Beta-2, etc.

In accordance with the invention, site preparation prior to theinsertion of a gene and/or growth factor into the body can occur at anyselected site. For example, examples of site preparation includedebridement of a burn wound, the application of EDTA or citric acid to abone site, or any other desired site preparation.

As used herein, genetic material includes a gene(s), a portion of agene, a growth factor(s), a gene product(s), and/or ECM whichindividually or collectively function to cause the genesis and growth ofan organ.

EXAMPLE 33

Example 18 is repeated except that the patient is a 24 year oldCaucasian male and the genetic carrier solution is injected into twosites in the right leg of the patient. The first site is on the exteriorwall on one side of the right leg artery. The second site is inside thewall of the right leg artery on the other side of the artery. The rightleg artery is not blocked and is a normal healthy artery. Similarresults are obtained, i.e., a new section of artery grows integral withthe original right leg artery, and a new section of artery growsadjacent the original right leg artery.

EXAMPLE 34

Example 18 is repeated except that VEGF growth factor is utilized in thegenetic carrier solution in place of the cDNA. Similar results areobtained.

EXAMPLE 35

Example 18 is repeated except that the patient is a 32 year oldCaucasian female, the cDNA produces a VEGF growth factor which promotesthe growth of veins, and the genetic carrier solution is injected intotwo sites in the right leg of the patient. The first site is on theexterior wall on one side of a large right leg vein. The second site isinside the wall of the right leg vein on the other side of the vein. Theright leg vein is not blocked and is a normal healthy artery. Similarresults are obtained, i.e., a new section of vein grows integral withthe original right leg vein, and a new section of vein grows adjacentthe original right leg vein.

EXAMPLE 36

Example 18 is repeated except that the patient is a 55 year oldCaucasian male, and the genetic carrier solution is injected into twosites in the coronary artery of the patient. The first site is on theexterior wall on one side of the artery. The second site is inside thewall of the artery on the other side of the artery. A section of theartery is damaged, is partially blocked, and has a weakened wall. Thefirst and second sites are each below the damaged section of the artery.Similar results are obtained, i.e., a new section of artery growsintegral with the original artery, and a new section of artery growsadjacent the original artery. The new section of artery has integrateditself at either end with the original artery so that blood flowsthrough the new section of artery.

1-5. (canceled)
 6. A method of growing a new portion of a pre-existingheart comprising the steps of placing a growth factor in a body of ahuman patient and growing new cardiac muscle and growing a new artery insaid heart.
 7. The method of claim 6, wherein said growth factorcomprises a multifactorial and non-specific cell.
 8. The method of claim6, wherein said growth factor is placed in said body by intravenousinjection.
 9. The method of claim 7, wherein said cell is placed in saidbody by intravenous injection.
 10. The method of claim 6, wherein saidgrowth factor is placed in said body by intraluminal injection.
 11. Themethod of claim 7, wherein said cell factor is placed in said body byintraluminal injection.
 12. The method of claim 6, wherein said growthfactor is placed in said body by an angioplasty balloon.
 13. The methodof claim 7, wherein said cell is placed in said body by an angioplastyballoon.
 14. A method of growing a new portion of a pre-existing heartcomprising locally placing a growth factor comprising a stem cell in abody of a human patient to grow new cardiac muscle in said heart. 15.The method of claim 14, wherein said stem cell is multifactorial andnon-specific.
 16. The method of claim 14, wherein said stem cell isplaced in said body by intravenous injection.
 17. The method of claim14, wherein said stem cell is placed in said body by intraluminalinjection.
 18. The method of claim 14, wherein said stem cell is placedin said body by an angioplasty balloon.